The discovery of insulin
Science entered the experimental period in the 19th century. This century was an important period for the development of most medical sciences. Oskar Minkowiski and Josef Von Mering wanted to know whether the pancreas was an internal organ necessary to maintain life. In 1889, they removed the pancreas from a dog. As a result, the dog ate more and became more hungry. Symptoms of drinking, polyuria, elevated blood sugar, and urinary sugar. This experiment clearly points out that the pancreas is related to diabetes. The pancreas may secrete a substance that lowers blood sugar, but where the substance that lowers blood sugar comes from the pancreas has always been a question. puzzle. A few years ago, there was a doctoral student named Paul Langerhans in Berlin, Germany. He discovered that there are groups of special cells in the pancreas, which can be separated from the pancreatic exocrine cells or pancreatic ducts. What are the functions of these cells? Langhans made no further statement. It was not until 1893 that Edouard Laguesse named these cells islets of Langerhans, believing that they were related to the endocrine secretion of the pancreas. In 1909, a Belgian physician, Jean de Meyer, believed that the islets of Langerhans might be the place where the blood sugar-lowering hormone was secreted, and named this hormone insulin.
Early Insulin Extraction
Since the pancreas is generally believed to contain substances that lower blood sugar, some scholars devoted themselves to the research of extracting substances from the pancreas that lower blood sugar in the early 20th century. There is a Berlin doctor named George Zuelzer. He found that some pancreatic extracts can reduce the urine glucose excretion of dogs after the pancreas is removed, and the acidosis can also be improved. Some of these extracts can even cause hypoglycemia in dogs, and one of his extracts has a U.S. patent (called Acomatol). In order to enrich the content of his research, it was still a few years late and it was not until 1907 that the research report was officially published. Although his pancreatic extract was used on eight diabetic patients, the clinical trials had to be terminated because the side effects were too great to overcome.
Nicolas Paulesco, a physician and professor of physiology in Bucharest, the capital of Romania, has also successfully extracted hypoglycemic substances from the pancreas of dogs and cows. The first time his extract was injected into a dog, the dog died of hypoglycemia. He named the extract Pancreine. Due to the impact of the outbreak of World War I, his research was not published until 1921, and Pancreine could not be used clinically due to fever and other serious side effects.
In 1919, Israel Kleiner of Rockefeller University in the United States systematically recorded a series of blood sugar changes in animals after administration of pancreatic extract. Unfortunately, he changed jobs later and changed his position. The facility was insufficiently equipped and there was no animal research room, so he had to terminate his research work in this area.
Successful Insulin Extraction
Frederick Grant Banting, a surgeon in Toronto, Canada, is a surgeon who is passionate about new inventions. At 2 o'clock in the night on December 30, 1920, he got an inspiration and wrote a simple paragraph in his notebook: "Diabetes, tie the pancreatic duct of the dog to degenerate the exocrine glands of the pancreas. You need to keep the dog alive, and then try to cure it." Separate endocrine secretions to reduce diabetes." Although Dr. Banting was a very skilled surgeon, he had no experience in diabetes or related research, so he consulted J.J.R. Macleod, a very prestigious professor of physiology at the University of Toronto at the time. In the summer of 1921 Macleod agreed to provide him with laboratory animals (dogs) and a student research assistant, Charles H Best.
Banting and Best's earliest research started with organ transplantation. They tied the pancreatic duct to separate the atrophied pancreas and transplanted it into diabetic dogs with the pancreas removed. However, they soon gave up this method because McLeod It was suggested that they cool the aspirated pancreas and inject it directly into the dog. After many experiments, Banting and Best found that the blood sugar-lowering effects of the whole pancreas extract and the atrophic pancreas extract after tying the pancreatic duct were equivalent, so they extracted directly from the pancreas without tying the pancreatic duct first. At Dr. Banting's request, Macleod invited James B Collip, a scholar with considerable biochemistry literacy, to join the research team in December. Banting and Best presented it orally at the American Physiological Society on December 30, 1921, and later wrote a paper published in J Laboratory & Clinical Medicine. Their findings were met with much skepticism at the time, and other side effects such as fever could not be addressed. The general assessment is that the result is no better than the previous results of Chu Zu, Paosco and Claire.
After joining this research team, Kelipu devoted himself to improving the extraction method and found that injecting pancreatic extract can increase liver glycogen storage and eliminate urinary ketones. On January 1, 1922, they injected the extract into a human for the first time. Leonard Thompson was 14 years old at the time. He had type 1 diabetes and was hospitalized at Toronto General Hospital. He was a frequent patient who died. After Thompson received an extract injection, his symptoms did not improve and a sterile abscess developed at the injection site. Kelipu continued to improve the extraction method. A few days later, on January 23, Thompson received another injection. As a result, his blood sugar returned to normal, and both urinary sugar and urinary ketones disappeared. It was such a simple clinical trial that opened a new era of insulin treatment for diabetes, saved the lives of countless patients with type 1 diabetes, and greatly improved the quality of life of diabetic patients.
At first, they named the hypoglycemic substance of pancreatic extract Isletin. Later, Macleod discovered that in 1909, the Belgian physician Mayer had named the substance that was only a hypothesis at the time (see above), so Just follow Mel's naming and change its name to Insulin. On May 3, 1922, they published their research results again at the American Physiological Society in Washington. The treatment they received was completely different from the last time. They received standing ovation from the full audience and were hailed as the greatest achievement of contemporary medicine.
After the invention of insulin, they encountered another problem. Wave after wave of people with type 1 diabetes are pouring into Toronto, and the output of the Kelipu laboratory extraction method cannot meet the demand. Later, they cooperated with Eli Lilly Co. of Indiana to mass-produce insulin commercially. With the consent of the patent owner, the University of Toronto, they also cooperated with Denmark and the United Kingdom to produce insulin. By 1923 Insulin will be available in North America and Europe in October. This year the Nobel Prize Committee also quickly selected Banting and MacLeod as the winners of the Medicine Prize. Banting announced that they would split their prize money equally between Best and McLeod equally between them and Collip. The relative merits, contributions, and winners of these four people's research on the invention of insulin were also debated at the time. Later generations generally believe that this research was a team effort. The motivation for the research originated from Banting and was helped by Best's work in the laboratory; McLeod was the leader of the entire study; Collip made a major breakthrough in the extraction method of insulin. , these four people should be officially awarded the Nobel Prize in Medicine together; the University of Toronto also played a major role in providing research funds, equipment and experimental animals. The research team split up after the discovery of insulin. MacLeod remained chairman of the Department of Physiology at the University of Toronto until his death in 1935. Banting was the director of the university's research department and died in a plane crash in 1941. Best later became a professor of physiology to continue diabetes research and actively participated in the establishment and development of the American Diabetes Association. He died in 1978. Collip moved to the University of Edmonton in Alberta and made an important contribution to the later discovery of parathyroid hormone. He died in 1965.
The first diabetic patient to receive insulin treatment, Thompson, died in 1935 and lived 13 years longer, something that would never have happened before the invention of insulin. At least two of the first diabetic patients treated with insulin in Toronto in 1922 died later than the four inventors of insulin, one of whom died in 1993 at the age of 76.