Source: New Scientist
Date: 4 March 2009

Japanese pioneer developed first general anaesthetic

by Stephanie Pain

Japanese anaesthesia pioneer Seishu Hanaoka
Pioneering Japanese surgeon Seishu Hanaoka, with his mother (left) and wife
(Image: International Museum of Surgical Science)

"When the dreadful steel was plunged into my breast... I began a scream that lasted unintermittingly during the whole time of the incision. I almost marvel that it rings not in my ears still, so excruciating was the agony."

When English writer Fanny Burney had surgery for breast cancer in 1811, she felt every move of the knife as the surgeon cut through her all too resistant flesh. The introduction of ether and chloroform as general anaesthetics was still 35 years away. Yet, unknown to doctors in the west, Japanese surgeon Seishu Hanaoka had performed the same operation several years earlier - and his patient hadn't felt a thing.

IT WAS nine months before Fanny Burney could bring herself to write about the operation to remove her breast. In a letter to her sister Esther, she described in harrowing detail what she had felt as the surgeon cut and scraped and cut some more. By the early 19th century, Europe's surgeons had the knowledge and skills to perform major operations. What they didn't have was an effective anaesthetic. Opium or copious amounts of cognac could help dull the pain, but no one had yet found a reliable way to render a patient unconscious during surgery - or so European surgeons thought.

Unknown to the rest of the world, on 13 October 1804, Japanese surgeon Seishu Hanaoka had put 60-year-old Kan Aiya under with a general anaesthetic in order to remove her cancerous breast. While Hanaoka's surgical technique owed much to western medicine, his anaesthetic was rooted firmly in the tradition of Chinese medicine that prevailed in Japan at the time. By combining the two, Hanaoka was able to perform surgery other Japanese doctors dared not try - and Europe's surgeons could perform only after tying down the patient and blocking out their screams.

Hanaoka was born in the small town of Hirayama in 1760, possibly the perfect time for a pioneering doctor. Worried by the spread of Christianity and angered by the activities of Portugal's Jesuit priests, Japan had expelled all Europeans in 1639. An exception was made for the Dutch, who were tolerated because they stuck to business and kept their religion to themselves. Even so, Dutch traders were confined to the tiny walled settlement of Dejima, an artificial island in Nagasaki Bay. Their activities were strictly controlled and their movements closely watched. All communication was through official Japanese interpreters, who ensured that foreign ideas did not slip in among the Dutch imports, but here too there was an exception.

Japan's doctors had always been curious about the medicine practised by the Jesuits. After they were expelled, the one window onto western medicine was at Dejima, and Dutch medical books were allowed to trickle into the country. Better still, the Dutch East India Company sent a succession of surgeons to Dejima. The interpreters watched them at work, took notes, and reported what they had seen. A few even took lessons. Soon, Japanese doctors began to try some of the simple surgery picked up from the Dutch, and schools of "Dutch-style surgery" began to spring up.

Despite its name, Dutch-style surgery bore only a passing resemblance to that practised in Europe. It was based on a handful of badly translated books and sketchy accounts of operations performed by a string of Dutch surgeons, some no more than ship's doctors. Japan's doctors were also highly selective in what they chose to adopt. One of the main tenets of Chinese medicine was to avoid harming the body, so while Japan's doctors followed Dutch advice on treating wounds and fractures, they rejected invasive surgical procedures. European doctors routinely amputated limbs, removed cataracts and extracted bladder stones. In Japan, even bloodletting was regarded as abhorrent.

In the 1740s, however, there was a big push to find out more about western science and medicine. The authorities actively encouraged "Dutch learning", and while earlier interpreters had learned just enough Dutch to do business, scholars were now exhorted to learn the language fluently enough to read and translate Dutch books.

By the time Hanaoka was beginning his medical studies in the 1780s, attitudes towards surgery were changing. What prompted the change was a book of anatomy. In Europe, anatomy was the foundation stone of medicine and its medical students pored over anatomy texts and dissected bodies. In Japan, students learned about the body from stylised drawings in ancient Chinese texts. Dissection of human bodies was forbidden.

In 1771, the revered doctor Genpaku Sugita, a proponent of Dutch learning, acquired a Dutch edition of Johann Kulmus's Anatomical Plates. Curious to find out how Kulmus's drawings compared with Chinese ideas of the body, Sugita and fellow doctor Ryotaku Maeno bribed an executioner to allow them to watch the dissection of a criminal - and took the book along with them. They were so impressed by the book's accuracy they spent the next four years translating it. Its appearance marked a turning point in Japanese medicine. No one could deny that Dutch surgery was based on sound knowledge of the body.

Following in his father's footsteps, Hanaoka left Hirayama in 1782 to study medicine in Kyoto. After studying traditional Chinese medicine, he took lessons in Dutch-style surgery, which by then was far more advanced than in his father's day. At 25 he took over his father's practice in Hirayama and immediately began work on his anaesthetic.

Hanaoka's great ambition was to save women from breast cancer by surgically removing their tumours, an operation he had seen in "a foreign book". But he also considered it his duty to prevent pain, and there the Dutch were no help at all. He could find no mention of anaesthesia in their books. Chinese medicine, by contrast, was well endowed with drugs that deadened pain, numbed sensation and induced sleep. Hanaoka wanted something that did all these things without killing the patient in the process.

That was a tall order. All these drugs came from extremely poisonous plants, and while some could safely be smeared onto skin to numb a small area before minor surgery, for more serious operations the drug would have to work on the whole body, which meant it would have to be swallowed.

It took 20 years of experiment before Hanaoka found the right formula. He started by combining different herbs at different doses, testing his draughts on cats and dogs. The difficulties were all too evident: if the drug wasn't powerful enough, the animals still felt pain; if it was too strong they suffered nerve damage or died. When he thought he had arrived at a safe dose, he tried it on his wife. She went blind, transforming a story of wifely devotion into one of medical heroism.

Hanaoka persisted and eventually found a formula that worked without inflicting terrible after-effects. He called it tsusensan. The key ingredients were Angel's trumpet (Datura metel) and monkshood (Aconitum japonicum). The first contains scopolamine, hyoscyamine and atropine, which are still used as sedatives and muscle relaxants, while monkshood contains aconitine, a powerful neurotoxin. To bolster the analgesic and sedative effects he added angelica, Szechuan lovage (Ligusticum wallichii) and the arum Arisaema serratum.

News of the experiments spread, and in 1804 Hanaoka finally achieved his ambition of performing cancer surgery under anaesthetic. Aiya, his first patient, had a large tumour in her left breast and had turned to Hanaoka in desperation. The anaesthetic worked, the operation was a success and Aiya went home. Sadly it came too late. Her cancer had spread and she died six months later.

Hanaoka went on to perform more than 150 similar operations and other procedures deemed too difficult by his contemporaries. Patients and students eager to learn his techniques flocked to Hirayama, and Hanaoka's place in Japanese history was assured. Yet Japan's policy of isolation meant the world outside remained ignorant of Hanaoka's anaesthetic. By the time Japan reopened its doors to foreigners, in 1853, they had no interest in it: they had finally found anaesthetics of their own.

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