Banting and the discovery of insulin

Banting and the discovery of insulin – İngilizce ileri düzey okuma parçası (advanced reading)

While at the Medical School, Banting went into the library and looked at the November issue of Surgery, Gynaecology and Obstetrics. The first article was entitled ‘The relation of the Islets of Langerhans to Diabetes’ by Dr. Moses Barron of Minneapolis. Banting had to talk to his students next day on the functions of the pancreas, so he took the journal home with him.

One paragraph in Barron’s review of previous literature on the subject referred to the experiments on tying the pancreatic ducts of rabbits made by Arnozen and Vaillard thirty-six years earlier. Banting had not heard of these experiments before, but he knew that attempts to treat diabetes with extracts of the pancreas had failed; and he wondered why.

A possible answer that occurred to him was that the hormone from the islets of Langerhans was destroyed during the extraction of the pancreas. The question then was what might destroy it; and his thoughts turned to the digestive ferment that the pancreas produced. He knew this was very powerful, so powerful that it could break up and dissolve all sorts of protein foods including the toughest meats. Perhaps, during the process of extraction, this ferment destroyed the vital hormone.
If that were so, Banting reasoned, the extraction ought to be delayed until the pancreas was no longer producing this ferment. According to the experiments of Arnozen and Vaillard, this condition could be reached by tying the pancreatic ducts. It was two o’clock in the morning of October 31, 1920, when he wrote in his small black notebook: ‘Tie off pancreas ducts of dogs. Wait six or eight weeks. Remove and extract.’

Although he did not know it, this was much the same idea that had come to Lydia de Witt fourteen years earlier. But it was not for the idea alone that Banting deserves to be remembered; his greatness lay in the way he put it into practice. He had to wait until the spring of 1921 before he could start work, and he filled in the time by reading all the literature on the subject he could find. He still missed Lydia de Witt’s work. At last he was given his laboratory-small, hot and rather primitive-and his ten dogs. His assistant, Charles Best, was a recent graduate in physiology and biochemistry who had been working under Macleod on sugars. They began work on May 16.

Banting began by tying off the pancreatic ducts of a number of dogs, which was quite easy. Then he had to remove the pancreas from other dogs to give them diabetes. The operation was not easy, and Banting’s training and ability as a surgeon proved invaluable. Even so, several dogs died before he evolved a suitable technique.

On July 6 Banting and Best chloroformed two of the dogs whose pancreatic ducts they had tied seven weeks earlier, and were disappointed to find that the pancreas had not degenerated as they had hoped. They had not tied the ducts with the correct degree of tension needed-the margin of error was very small. And they had only one week left to complete their work. Macleod was away in Europe, but an extension was granted by the authorities, and the experiment was continued. On July 27 another duct-tied dog was chloroformed, and when Banting operated he found that the pancreas had shrivelled to about one-third of its original size. It was removed, chopped into pieces and mixed with saline; and a small amount of a filtered extract was injected into one of the diabetic dogs. Within two hours its blood sugar had fallen considerably, and before long the dog became conscious, rose, and wagged its tail.

The effect of the injection was so dramatic that Banting and Best could hardly believe it; but further experiments made them sure that they had indeed found what they were looking for. They had succeeded in extracting the anti-diabetic hormone secreted by the islets of Langerhans. They called it ‘isletin’. It was some time later that Macleod renamed it insulin, a word that had been suggested in 1910. Insulin did not cure diabetes. After a while the dog relapsed, and further injections were needed to revive it again. But with regular injections of insulin a dog with diabetes could live.

Banting and Best next succeeded in obtaining insulin by injecting secretin to stimulate the production of the digestive ferment from the pancreas and exhaust the cells from which it came. This was a much quicker method than tying the ducts and waiting several weeks; and although the practical results were disappointing, its importance to the theory was considerable.

So far insulin had been extracted only in sufficient quantity for laboratory work, and already Banting and Best were seeking means of getting larger supplies. They now obtained insulin from the pancreas of a foetal calf-that is, a calf that had not yet been born. Nature, ever practical, does not supply digestive ferments until a calf starts eating, so there was nothing to destroy the insulin during extraction. This new success enabled Banting and Best to keep up an adequate supply of insulin for more extensive experiments. At the same time they realized that if their work was to have practical results in medical treatment it would be necessary to get much larger supplies. And they could only come from adult cattle in the slaughterhouse. The problem was to find a means of extracting the insulin from the pancreas of an ordinary adult animal.

The problem was solved well enough to provide insulin for the first injections on human beings. Two patients in Toronto General Hospital were chosen-a fourteen-year-old boy and a doctor, both very seriously ill with diabetes: ‘hopeless’ cases. When treated with insulin-although still in a relatively impure form-they improved at once. The boy is alive and well to-day.

‘Research in medicine is specialized,’ Banting said later, ‘and as in all organized walks of life, a division of labour is necessary. In consequence, a division of labour in the field of insulin took place.’ Professor J. B. Collip, a biochemist, was called in to produce a purer extract. He succeeded very quickly; and other workers made it possible to obtain insulin on a really large scale. Before very long insulin injections became the standard treatment for diabetes all over the world. They still are today.
Banting, only thirty-one years old, was suddenly famous. Although for some extraordinary reason he was not knighted until 1934, he was awarded the Nobel Prize for Medicine in 1923jointly with Macleod.

(Fom Chapter VIII of Great Discoveries in Modern Science by Patrick Pringle.)