Near the beginning of the 3rd century in ancient China, Han Dynasty leader Cao Cao is said to have called upon a famous doctor named Hua Tuo to treat a headache. Cao Cao had received said headache from a hallucinatory dream that occurred after attacking a sacred tree with his sword, according to the classic 14th century historical novel Romance of the Three Kingdoms.

Hua Tuo, known today as the father of Chinese surgery, was already famous for treating a number of other patients successfully. Historical accounts credit him for his fame with acupuncture, surgery and for the use of an herbal drug mixture (possibly including marijuana or opium), which made him one of the first known doctors in the world to use anesthetics. The surgeon took the warlord's pulse and determined a tumor was to blame. Then Hua Tuo made his best medical recommendation: Cao Cao needed to get a hole drilled in his head.

If the story is true, it could be one of the earliest cases of trepanation documented in Chinese literature. But it turns out that this was far from the oldest example of the practice in the archaeological record. A recent research review published in World Neurosurgery finds that trepanation may have been happening in China far earlier than commonly understood, in one case dating back to at least 1,600 B.C.

“From what we found, there is a good amount of archaeological evidence as well as literary evidence to support the fact that this was also done in ancient China, not just in other parts of the world,” says Emanuela Binello, a neurosurgeon at Boston University’s School of Medicine and the senior author of the review. “It’s really a global phenomenon. It was happening everywhere back then.”

For those unfamiliar with the Darren Aronofsky surrealist film Pi (spoiler alert), trepanation involves literally drilling or scraping a hole in the skull, usually for medical reasons. In Europe the process was described early on by famed Greek doctor Hippocrates, and later by the Roman physician Galen. Researchers say that the success rate of these operations is low, as it can cause infection or worse—especially if the dura mater, the thick membrane that sits between the skull and brain, is breached. But in some cases, removing a piece of skull can relieve pressure on the brain induced from head injuries.

Despite its inherent risk, the practice continued in Europe more or less linearly through the Medieval period; Dutch artist Hieronymus Bosch and others painted several scenes depicting trepanation more than 500 years ago. Archaeological evidence has taken dated the practice back much farther in places like ancient America and Africa, and a recent dig by a Polish archaeologist claimed to have found a 7,000-year-old case in Sudan.

But details of the practice in China are blurry, due in large part to language barriers. So Binello, who was initially surprised she had not seen much evidence of the practice in China, set out to look deeper into trepanation in the Far East. She and her Chinese-speaking coauthor Leah Hobert, also at the Boston University medicine department, sifted through everything from Chinese news articles on archaeological discoveries to ancient literary and historical sources that describe or make mention of opening up people’s skulls.

Aside from the semi-mythical case of Hua Tuo, who Binello describes as “the Chinese patron of medicine and surgery,” Binello discusses other operations in her review, including some mention of surgically exposing the brain in the Esoteric Scripture of the Yellow Emperor, dating as far back as the 5th century B.C. and describing legendary characters going back to the 3rd millennium B.C., and later accounts of a metal worker trepanning a leper's brain to remove a cupful of worms or parasites.

One of the oldest archaeological cases dates back to a mummified woman in the Xiaohe tomb, discovered in the 1930s and excavated in 2005, which dates back to around 1,615 B.C. in the Xinjiang Uygur autonomous region. “The extent of the tissue healing around this craniotomy site suggests that she lived at least one month after the craniotomy was done,” Binello says.

The fact that the woman survived the operation, and that other cases Binello found show signs of healing such as smooth edges around the hole, is significant. She says that the prevalence of people who survived the opening suggests that the damage wasn’t made by traumatic injury like getting hit on the head with a spiked bat. But John Verano, an anthropology professor at Tulane University in New Orleans who has studied trepanation extensively in ancient Andean cultures, thinks Binello’s review made too many sweeping assumptions.

A key problem, he says, is the lack of evidence of people who didn’t survive trepanation. “The idea that the Chinese would have 100 percent success rate, at least based on the samples they’re describing, is pretty unlikely,” he said, adding that the skulls that show no survival are better for proving trepanation because you can still see actual unhealed tool marks. Studies he’s conducted show different things can appear to be trepanation, including injury, fracture, congenital disorder and even rodent chewing. “It seems everybody finds a skull with a healed hole in it and they say it’s trepanation.”

Verano, who published a book this year about the practice in the Andes, has recorded upwards of 800 cases of trepanation in Peru and Bolivia. That's more believable cases than the rest of the world combined, he believes. These cases include skulls that show no survival, short-term survival and longer survival after the hole was made, from around 400 B.C. in the central Peruvian highlands right up until a few isolated cases that popped up in the early 2th century.

In Europe, the reasons for trepanation varied, he says. “In medieval Europe there was an idea that insanity might be represented by rocks in your brain, or the devil in your brain and you could drill a hole in somebody’s skull and maybe release the demons,” he says.

But almost everywhere else in the world, including Peru, the operations were conducted to try to fix physical issues. “It was a practical medical procedure for reducing pressure on the brain, for cleaning wounds and perhaps stopping bleeding from hemorrhages and such, ” he says. In the early days it was dangerous, with a 40 percent mortality rate, though this death rate dropped to 15 percent by Inca times in the 13th to 16th centuries, he says.

In the 18th and 19th century, archaeological specimens of trepanation are conspicuously near-absent in China. Binello has an explanation: During that period, trepanation (and in fact surgery in general) fell out of favor as practices like acupuncture and other traditional herbal remedies were deemed better than a hole in the head. He suspects the reasons could be due to Confucian beliefs that hold that the body was sacred, and shouldn’t be mutilated in life or death.

After these very early descriptions, archaeologists and historians have recovered little to no evidence of neurosurgical procedures, Binello says, adding, “of course that doesn’t mean it wasn’t going on, just that we couldn’t find it.” Verano adds that cultural taboo could have driven the practice underground in parts of China, and that while he doesn’t believe it was necessarily widespread, the idea of trepanning certainly could have gotten into some people’s heads. He notes that healers have conducted trepanning operations under the radar in Kenya fairly recently with tools like a pocket knife or even a nail where access to neurosurgeons is limited.

Something similar could have occurred in parts of China throughout history, where cleaning head wounds and removing bone fragments could have progressed to removing parts of skull to relieve pressure on the brain, he says. If that's true, it could mean that brain surgery may have developed much earlier in China before cultural shifts in thinking put a halt on the practice. As it stands now, Binello says that the Chinese did not go back to drilling holes in living skulls for treatment again with any frequency until Mao Zedong took power and started to send Chinese doctors to train in the west in the 20th century.

“It was a very late development, ” she says.

Unfortunately for the case of Chinese trepanation, Hua Tuo’s case will likely provide no more evidence. The Romance of the Three Kingdoms holds that Cao Cao became suspicious of Hua Tuo's surgery suggestion, and decided to have him executed as an assassin. After his death, even historical sources say that his medical notes were burned after he was killed. “Hua Tuo was executed and the [prison] guard gave it to his wife who used it to light a fire, so all Hua Tuo’s medical pearls were lost,” Binello says.