How We Discovered Insulin
By CHARLES H. BEST, M.D., as told to J.D.Ratcliff
“Let’s get started, Mr. Best,” he said. “We rally haven’t much time.” What an understatement! He had asked the University of Toronto for the use of a laboratory for eight weeks, for ten dogs, and for the help of someone who knew chemistry and physiology. The money value of his modest request was $100. With this he thought he could conquer a disease that had always baffled medical men: the merciless killer, diabetes.
“You read French, don’t you?” Banting asked. I did. “Let’s to the library then.” He said, “and look up how a Frenchman named Hedon took a pancreas out of a dog.”
That was the beginning.
We both knew the horror of diabetes—described by a Greek physician 2000 years earlier as “a disease in which the flesh melts away and is siphoned off in the urine.” Somehow the bodies of stricken people stopped burning sugar into energy. Instead their bodies turned cannibal, consuming stored fats and proteins. There was always unquenchable thirst—victims often drinking several gallons of water a day while losing a like amount of sugary urine. And their appetite was ravenous. The only treatment was a rigid diet designed for correct the patient’s disrupted chemical balance. Severely stricken victims were offered a grim choice: eat well today ad die tomorrow, of cut down to a few hundred calories a day and linger for a white in weary befuddlement.
Banting had seen diabetes convert a cicacious 15-year-old girl classmate at Alliston, Ontario, into a pathetic child for whom death came swiftly. At my home in West Pembroke, Maine, I had seen the same happen to my Aunt Anna. A stout, vigorous woman in her early 30s, she wasted to 80 pounds before she died.
The world would have considered us a most unlikely pair to match wits with this killer. I was a 22-year-old graduate student, working for my master’s degree in physiology and biochemistry. Banting’s experience in research was virtually nil. At his family’s urging he had started out to study for the Methodist ministry. But, a halting speaker, he changed to medicine. He had been an average student.
After serving as a surgeon in the Canadian army in World War 1, and winning the military Cross for bravery, he set up practice as an orthopedic surgeon in London, Ontario. He waited for patients who never came. One month his income was four dollars. His fiancée could see little future with such a man, and they parted.
Noël this man was staking all his meager resources on his hunch that he could cure the sugar sickness. He gave up his little practice, sold his office furniture, books, instruments, everything. Banting couldn’t afford another failure.
It was known that the pancreas—a pale-yellow, pollywog shaped abdominal organ that produces digestive juices—was somehow involved in the disease. In 1889 Oscar Minkowski in Germany had removed a dog’s pancreas, mainly to see if the animal could get along without it. Next day he noted flies clustered around puddles of the dog’s urine. The urine was sugary; the dog, in normal health the day before, now had diabetes.
Did pancreatic juices, then, contain a factor that normally regulated the metabolism of sugars? To test the idea, research men tied off the ducts that carry these juices to the intestine. When dogs got this surgery, their pancreases shriveled and generated—but they did not Ger. diabetes! The shriveled organs, unable to send digestive secretions to the intestines, were still producing the anti-diabetic factor.
But if it wasn’t in the pancreatic juices, where was it?
Attention shifted to the thousands of mysterious little “islet” cells scattered through the pancreas and surrounded by tiny capillaries. Did they secrete some “X” stuff, perhaps a hormone that regulated the burning of sugar? And did they empty it, then, not into the intestine but into the blood stream? Several research men had suggested as much and had gone hunting for the elusive hormone. But all had come home with empty game bags.
Now it was our turn.
“Maybe it’s this way, Mr. Best.” Banting did not say—nor for several days would we become Fred and Charley. “Maybe when the researchers remove a healthy pancreas and grind it up to extract this X stuff, enzymes in the digestive juice mix with the X stuff and destroy it—just as they break down proteins in the intestine. Maybe that’s why no one has been able to find it.”
Knowing that when the pancreatic ducts are tied off the cells, which secrete digestive juices, degenerate faster than do the islet cells, we would tie of these ducts in dogs and wait. “In seven to ten weeks the pancreas will degenerate, stop making digestive juices—and there will be nothing to destroy the X stuff. You extract it. Then we’ll give this extract to the diabetic dog and see if it lower the sugar in blood and urine.”
I did my chemical work in our cubbyhole lab. Dog surgery was performed two flights up in the sky lighted artic. Before summer was over, that attic became steamy as any Turkish bath. To get some relief we wore little of nothing under our white lab coats. Since money was short, we ate in the lab. Eggs and sausage fried over a Bunsen burner became diet staples.
One serious problem was a scarcity of dogs. When the situation became acute, Banting said, “Crank up the Pancreas, Charley, and let’s go.” [This was our name for hid Model T Ford.] We rattled through the poorer parts of Toronto, hunting for dogs whose owners would part with them for a dollar.
We had tied off the first pancreatic ducts in May, and in early June we expected the pancreas to be shriveled, the X stuff accessible. We opened one of the animals—and found the pancreas blooming with health, no atrophy, no shriveling. Banting and I had tied the ducts incorrectly.
Our eight weeks were almost up. But Banting was a stubborn man. During the war he had gotten ugly shrapnel wound in hi right arm. Doctors had wanted to amputate. Banting refused—and nursed the arm back to health. Now we were going to nurse our sickly project back to health.
Professor John J.R. McLeod, head of the physiology department, who had provided us with work facilities, was on vacation in Europe. “He won’t know the difference if we way on.” We decided.
We began reporting on dogs, tying off ducts, correctly this time. On July 27 we got the beautifully shriveled, degenerated pancreas we wanted. It should contain the X stuff—if the X stuff existed.
Now we sliced the pancreas into a chilled motor containing Ringer’s solution and froze the mixture. We allowed it to thaw slowly, ground it up and filtered in through paper. A dying diabetic dog was waiting; too weak of lift his head. Fred injected 5c.c. Of the filtrate into a vein. The dog looked a little better—but self-diffusion is easy such times. Blood tests were needed.
I drew a few droplets from the dog’s paw and began testing for blood sugar. Banting hovered over me. If sugar were heavily present the reagent in the test tube would turn deep red; little sugar and it would be a pale pink. There was a new test every hour and the reagent was getting paler, paler. Blood sugar was going down—form 0.20 percent, to 0.02 percent, to … it was headed for a normal 0.09 percent! This was the most exciting moment of Banting’s life or my own.
Life now became a blurred nightmare of work. This thing had to be nailed down. Dogs had to be injected, blood had to be drawn for testing, urine collected. It was an hourly, round the-clock schedule. We stretched out on lab benches to get what sleep we could.
But there was an ever-reviving miracle for us to behold: dogs glassy-eyed with the sleep of death upon them; then, a few hours later, they were up, tails wagging. Jolted back to life, one dog lived 12 days, another 22 days.
Our pet was Marjorie—dog number 33. Black-and-white, vaguely collie, she learned to jump up on a bench, hold out her paw to give us a blood sample and keep still to get the shot on which her life depended. For 70 days she was alive, well. Then we ran out of the extract, isletin, as we then called it. [Only later did McLeod persuade us to change the name of insulin]
It took almost all the isletin we could extract from a degenerated pancreas to keep one dog alive for one day. How far would this to toward keeping alive millions of diabetics around the world?
Fred remembered reading that the pancreas of an unborn animal was a mainle islet cell—since the digestive juice wasn’t needed in the womb. As a farm boy, he also knew that farmers frequently bred cows before sending them to the slaughterhouse, to hoist weight. Wouldn’t pancreases from the unborn calves be rich in isletin? We cranked up The Pancreas and headed for a slaughterhouse. Later, back at the lab, we ground up the salvaged pancreas, extracted, purified and reaped a rich harvest of isletin.
We could now keep dogs alive as long as we wanted. Eventually, of course, it was found that with improved extraction methods any animal pancreas—sheep, hog, and cow—provided insulin. There was going to be enough for all needs.
By November 14 we were ready to share some of our experiment with the world. Before the Journal Club of the Department of Physiology, Banting and I gave our first paper—complete with lanternslides showing blood-sugar charts. But the crucial question we had to be answered. Would insulin work in human beings?
Across the street in Toronto General Hospital was the 14-year old Leonard Thompson. After two years with diabetes, he was down to 65 pounds, had scarcely the strength of lift his head from pillow. By the usual criteria he would have, at most only a few weeks left.
We had established that insulin “cocktail” taken by mouth, did not work. So now Banting and I rolled up our sleeves. I injected him with our extract and he injected me—we had to be sure it wasn’t too toxic to be tolerated by human beings. Next day we had slightly sore arms that were all.
So in January 1922, the wasted little arm of the dying boy was injected. Testing began. All over again, it was the story of our dogs. Blood sugar dropped—dramatically. Leonard began to eat normal meals. Sunken cheeks filled out, new life came to weary muscles. Leonard was going to live! [He lived another 13 years and died in 1935—of pneumonia following a motorcycle accident]. He was the first of dozens, then hundreds, thousands, and millions to get insulin.
Honors began to shower on us. For the best piece of research conducted at the university that year we were awarded the Reeve Prize—a welcome $50. A grateful Parliament voted Banting a life annuity of $7500. Then came a great research institute named for him, and later one named for me. When Banting won the Nobel Prize in 1923 he shared the money equally with me.
Both of us stayed on at the university, and through the succeeding years concentrated on our individual research projects. But the excitement of the old days was missing. Then on a wintry February day in 1941, we were walking across the campus. “Charley,” said Banting, “let’s start working together again. You handle the chemistry, and I’ll….”
It was not to be. Three days later Banting—now a Major Sir Frederick Banting, working on problems of aviation medicine—was aboard a two-engine bomber bound for England. The plane crashed in a snowstorm in a forest near Margraves Harbor, Newfoundland. Banding, with a lung punctured by crushed ribs, used his waning strength to bandage the wounds of the pilot, the only survivor. Then he lay down on pine burghs in the snow and went into the sleep from which he never awakens.
Of all eulogies, perhaps most moving was the one spoken five years at a London gathering of the Diabetics association: “without Banting this meeting could have been only a gathering of ghosts bemoaning their fate.
