About Us
Frederick Grant Banting
The Discovery of Insulin
|
Frederick Grant Banting was born on November 14, 1891 at Alliston, Ontario, Canada, the youngest of five children of William Thompson Banting and Margaret Grant. He was educated at the Public and High Schools at Alliston, and later in 1912, pressured by his father a devout Methodist, he went to the University of Toronto to study divinity. He soon realised this was not the career he wished to follow and transferred to the study of medicine. In 1916 he achieved his M.B degree and then joined the Canadian Army Medical Corps, serving in the First World War in France. He was wounded at the battle of Cambrai and in 1919 was awarded the Military Cross for heroism under fire. |
|
After the war, Banting returned to Canada and for a short time practised as a doctor at London, Ontario. He studied orthopaedic medicine and during the year 1919-1920 was Resident Surgeon at the Hospital for Sick Children in Toronto. From 1920 until 1921 he taught orthopaedics part-time at the University of Western Ontario as well as continuing in general practice, and between 1921 and 1922 he lectured in Pharmacology at the University of Toronto, gaining his M.D. degree, together with a gold medal in 1922. During these years, Banting had become interested in diabetes. He knew from the works of Naunyn, Minkowksi, Opie, Schafer and others, that they had indicated diabetes was caused by lack of a protein hormone secreted by the islands of Langerhans in the pancreas. Schafer had given this protein the name of insulin, and it was believed that insulin controls the metabolism of sugar, so that the lack of it results in an accumulation of sugar in the blood and the excretion of the excess sugar in the urine. Attempts had been made to supply the missing insulin by feeding patients with extracts of fresh pancreas, but these experiments had failed, possibly because the protein insulin had been destroyed by the proteolytic enzyme of the pancreas. Along with his predecessors, Banting was confronted with the problem of how to extract insulin from the pancreas before it had been destroyed. On October 31, 1920, whilst pondering over this problem, he came across an article on pancreatic duct-blockage by Moses Baron in a medical journal. Baron pointed out that when the pancreatic duct was experimentally closed by ligatures, the cells of the pancreas which secrete trypsin degenerate, but the islands of Langerhans remain intact. This gave Banting the idea that ligation of the pancreatic duct would, by destroying the cells which secrete trypsin, avoid the destruction of the insulin. Banting reasoned that after sufficient time had been allowed for degeneration of the trypsin-secreting cells, insulin might be extracted from the intact islands of Langerhans. This investigation had been tried before, but the article did not mention it and Banting was not aware of previous experiments. He wrote in his note book: Diabetus
|
|
|
Banting was determined to investigate this possibility. He discussed it with various people and
on November 8th, managed to arrange a meeting with J.J.R. Macleod, Professor of Physiology at the
University of Toronto. In the past, Macleod had discouraged several scientists in the field of
pancreatic extracts, but Banting was so enthusiastic that he offered him a laboratory and some
animals over the next summer holiday period. With the help of a student, Charles Best, as
his research assistant, Banting decided to take Macleod up on his offer and on May 17th, 1921,
the first dogs were depancreatised. Macleod advised Banting to use Hedon's method of
pancreatectomy and leave a small piece grafted under the skin to be removed later.
The first pancreatic extract was prepared and tested on July 30th, but with only temporary success, the dog died a day later. The pancreas they used had been removed seven weeks previously and left to degenerate. The second dog, brought back from a coma, also died within a day. In order to speed up the experiments, a full pancreatectomy was tried on August 3rd, after which Hedon's procedure was not used again. Banting and Best named their preparation 'Isletin' in notes on the experiments on the dog that had the first total pancretectomy. Testing the urine sometimes proved to be difficult, because its volume decreased after injections of the extract and in some cases, urination stopped altogether. However, during the second decade of the twentieth century, methods of blood-sugar testing had been developed and improved and were more accurate than urine sampling. These tests made diabetes research more reliable and efficient. On August 17th, 1921, another time-saving idea was tested; extracts of fresh, non-degenerated pancreas. Banting and Best did not recognise the positive results and continued with their faulty hypothesis that degeneration of the pancreas was necessary to obtain pure internal secretion. Boiling extract caused it to become inactive; exhausting the pancreas' external secretion with secretin was too effective. Extracts prepared with secretin lowered blood-sugar quickly, but caused profound shock. Many control experiments were carried out, for example in vitro sugar-burning capacity and checking the activity of mixtures with trypsin. Macleod was aware that thorough testing needed to be extended so that it was impossible for critics and pessimists to deny the positive effects. The experiments involved pre-injection blood tests, more frequent blood sampling after injection so that the effect was not missed, and establishing that it was a real blood-sugar lowering effect rather than dilution phenomena caused by the injections of reasonably large amounts of extracts. During the first half of September 1921, Banting and Best tested different ways of injecting. Rectal injections had no effect, but subsequent intravenous injections did prove to be effective. On September 17th, injections were given subcutaneously for the first time, but the results were unsatisfactory and Banting and Best decided it was not worth trying again until they had trypsin-free extracts. By the end of September, two more respected Toronto doctors/scientists, Starr and Henderson became involved in an attempt to continue the research by providing laboratory space and money. Between October and December 1921, Best read a publication by Paulesco from July 1921. The blood-sugar data, that he quoted, was so different from the generally accepted values for hyperglycaemia that Best was not impressed and ignored the information in the article. In February 1922, Banting and Best published their first paper describing their work up to November 10th, concluding that although they had “always observed a distinct improvement in the clinical condition of diabetic dogs after administration of extract of degenerated pancreas”; it was still too early for clinical trials. By that time, they had started a 'longevity' experiment, keeping a pancreatectomised dog alive for as long as possible. A visiting biochemist, Collip, who was interested in the ongoing investigations, became involved in designing better experiments. Banting had discovered information about foetal pancreases, from which active extracts could be prepared without ligation or degeneration, as the content of ancinar tissue was fairly low. Because of this, a plentiful amount of extract could be produced from fresh, whole foetal pancreas. New bacterial filtering methods produced more sterile extracts and subcutaneous injections became possible, spreading action over a longer period, so preventing shock. Because the group were becoming impatient and wanted to start clinical testing, on November 23rd, Banting agreed to be injected subcutaneously with 1 ½ cc of Berkefeld filtered extract. The extract did not have any harmful effects, but blood-sugar was not measured. One of the longevity experiments ended on December 2nd, when the dog died after convulsions, due to anaphylactic shock, although it now thought possible that it could have been hypoglycaemic shock, as more extract appeared to make it worse. Four days later the next longevity experiment commenced in which the extraction was performed with alcohol instead of aqueous saline, being easier to evaporate in order to concentrate the extract. This lead to the idea that the 'active principle' could be extracted from adult pancreases with alcohol too, these being available more cheaply than foetal pancreases. Although Banting and Best had already started using alcohol and adult pancreases before Collip joined them, his experience and expertise was a great asset. He started using rabbits and discovered that even the blood-sugar in healthy animals was lowered when given the extract. He also discovered that the residue and not the filtrate of a final filtering step contained the really powerful 'active principle'. On December 20th, 1921, Joe Gilchrist received tested, potent extract by mouth, with no benefit after a day. At that time, was not yet established that only injections would work. Because Collip was a much more experienced and thorough researcher, his results were better received than those produced by Banting and Best. More and more people became involved with the experiments and Banting felt he had been overtaken and his idea had been removed from his control, causing bad feeling within the group, and their relationship deteriorated. Because of the animosity, Banting and Best decided to have the first official test on a 14-year-old boy, Leonard Thompson on January 11th 1922. It was too early and the extract did not perform well. Collip had discovered the 'active principle' could be purified to a certain extent by gradually precipitating other protein with increasing amounts of alcohol. Only at around 90% alcohol the active principle would precipitate, leaving it pure enough not to cause abscesses at injection sites. Collip performed his first clinical test on the young Leonard Thomson on 23rd January 1922 which proved to be successful. Two days after the test, the group put their disagreements behind them and signed an agreement to work as a group again rather than trying to compete with each other. During February 1922, more clinical tests were carried out with favourable results. At the same time, without knowing the work being done in Toronto, Paulesco started clinical trials independently. In April, the Latin-rooted name 'insulin' was proposed – having already been suggested twice before, in 1909 and again in 1916, by two independent scientists and not known to the group in Toronto. On May 3rd, 1922, Macleod officially announced the discovery of insulin to the medical world. It took another six years for Wintersteiner to establish that insulin is a protein, and it was not until 1955 that Sanger and his co-workers explained the primary structure of insulin. (Note: See Sanger's Nobel Prize Lecture) In 1922 Banting was appointed Senior Demonstrator in Medicine at the University of Toronto and in 1923 was elected to the Banting and Best Chair of Medical Research, endowed by the Legislature of the Province of Ontario. He was also appointed Honorary Consulting Physician to the Toronto General Hospital, the Hospital for Sick Children and the Toronto Western Hospital. In the Banting and Best Institute he dealt with problems of silicosis, cancer and the mechanism of drowning and how to counteract it. In addition to his medical degree, Banting also received various other degrees and prizes, including a Life's Annuity of $7,500, which he received from the Canadian Parliament. On October 25th, 1923 Dr. Banting and his colleague Professor Macleod were awarded the Nobel Prize in Physiology or Medicine. Banting shared his award with Best and Macleod shared his with Dr. Collip. In 1924 he married Marion Robertson, they had one child, William, born in 1928, but the marriage ended in divorce in 1932. He married again in 1937 to Henrietta Ball. In 1928 Banting gave the Cameron Lecture in Edinburgh and was appointed member of numerous medical academies and societies both in his own country and abroad, including the British and American Physiological Societies and the American Pharmacological Society. In 1934 he was knighted, becoming Sir Frederick Banting. When the Second World War broke out he served as liaison officer between the British and North American medical services, taking a great interest in problems connected with flying, such as blackout. On February 21st, 1941, whilst en route to England, he was killed in an air disaster over Newfoundland. Since 1922 and the discoveries and efforts of Banting, Best, Macleod and Collip a great deal of research has gone into the improvement of insulin therapy, both in terms of improved insulin preparations and ease of use. In 1944 the standard insulin syringe was developed, helping to make diabetes management more uniform, and in 1955 oral drugs were introduced to help lower blood glucose levels. In 1959 two major types of diabetes were recognised; Type 1, insulin dependent diabetes and Type 2, non-insulin dependent diabetes. In the 1960s the purity of insulin was improved yet again and home testing for sugar levels in urine increased the level of control for people with diabetes. In 1966, the first pancreas transplant was performed at the University of Saskatchewan and in 1970, blood glucose meters and insulin pumps were developed and laser therapy was first used to help slow down or prevent blindness in people suffering with diabetes. In 1983 the first biosynthetic human insulin was introduced, followed in 1986 by the insulin pen delivery system. In the 80 years since the discovery of insulin, the guidelines for the treatment and control of diabetes is continually improving. |
|
|
Acknowledgements
The History of Diabetes Discovering Insulin Frederick G Banting – Biography |
|