Science entered the experimental stage in the19th century, and this century is an important period for the development of most medical sciences. Oskar Minkowski and Josef von Mering want to know whether the pancreas is an essential viscera for life. They removed the pancreas of a dog on 1889, and the dog showed symptoms of eating, drinking, polyuria, elevated blood sugar and urine sugar. This experiment clearly points out that the pancreas is related to diabetes. The pancreas may secrete a hypoglycemic substance, but the hypoglycemic substance comes from the pancreas. A few years ago, there was a doctoral student named Langens in Berlin, Germany. He found that there were clumps of special cells in the pancreas, which could be separated from exocrine cells or pancreatic duct. What are the functions of these cells? Langens made no further statement. It was not until 1893 that Edouard Laguesse named these cells Langshi Island, which was considered to be related to pancreatic endocrine. From 65438 to 0909, Jean de Meyer, a Belgian physician, thought that Langerhans Island might be the place where hypoglycemic hormone was secreted and named it insulin.

Early insulin extraction

Since it is generally believed that the pancreas contains hypoglycemic substances, scholars have devoted themselves to the research of extracting hypoglycemic substances from the pancreas since the beginning of the twentieth century. A doctor named George Zuelzer in Berlin found that some pancreatic extracts can reduce urine glucose excretion and improve acidosis in dogs after pancreatectomy. Some of these extracts can even lead to low blood sugar in dogs, and one of his extracts has been patented in the United States (called Acomatol). In order to enrich the research content, a few years later, the research report was officially published in 1907. Although his pancreatic extract was used in 8 diabetic patients, the side effects were too great to overcome, so he had to terminate the clinical trial.

Nicolas Lesko, a physician and professor of physiology in Bucharest, Romania, also successfully extracted hypoglycemic substances from the pancreas of dogs and cattle. The first time I injected the extract into the dog, it died of hypoglycemia. He named this extract pancreatin. Influenced by the outbreak of World War I, his research was published as late as 192 1 year, and Pankling could not be used in clinic because of serious side effects such as fever.

Israel Kleiner of Rockefeller University in the United States recorded a series of blood sugar changes in animals after beating pancreatic extract at 19 19. Unfortunately, he had to stop his research work in this field because of changing jobs, lack of equipment and no animal laboratory in the new place.

Successfully extracted insulin.

Frederick Grant Wanzin of Toronto, Canada, is a surgeon who is keen on new inventions. 1920 12.30 at 2 o'clock in the middle of the night, he had a brainwave and wrote a simple sentence in his notebook: "Diabetes, tie up the pancreatic duct of the dog, let the exocrine gland of the pancreas degenerate, let the dog live, and then try to separate endocrine secretions and reduce diabetes." Although Dr. Banting is a very skilled surgeon, he has no experience in diabetes and related research, so he went to consult J.J.R mcleod, a professor of physiology at the University of Toronto at that time. 192 1 summer, mcleod agreed to provide his laboratory, experimental animals (dogs) and a student research assistant, Charles H. Best. Banting and Best's earliest research began with organ transplantation. They ligated the pancreatic duct, isolated the atrophic pancreas and transplanted it into diabetic dogs with pancreatectomy, but they soon gave up this method because mcleod suggested that they cool the extract of atrophic pancreas and inject it directly into dogs. After many experiments, Wanjin and Best found that the whole pancreatic extract and atrophic pancreatic extract had the same hypoglycemic effect after being bound to the pancreatic duct, so they extracted it directly from the pancreas without binding the pancreatic duct first. At the request of Dr. Banting, mcleod invited James B. Collip, a scholar with considerable biochemical literacy, to join the research team in1February. Ban Ting and Best gave an oral report at the American Physiological Society on February 30th, 192 165438, and later at J Laboratory &; Clinical medicine. At that time, their research results were questioned, and other side effects such as fever could not be solved. Overall, the results are not better than those of Zubo Skoclaire.

After joining this research team, Klip devoted himself to improving the extraction method, and found that injection of pancreatic extract could increase the storage of glycogen in the liver and make urine ketone disappear. 1 922 65438+1October1,they injected the extract into human body for the first time. Leonard Thompson was 14 years old. He has 1 type diabetes and is hospitalized in Toronto General Hospital. He often dies. After receiving the injection of the extract, his symptoms did not improve, and aseptic abscess appeared at the injection site. Klip continued to improve the extraction method, and a few days later, on June 23rd, 65438, Thompson was injected again. Results Blood sugar returned to normal and urine sugar and urine ketone disappeared. It is such a simple clinical trial that opened a new era of insulin therapy for diabetes, saved the lives of countless 1 type diabetic patients and greatly improved the quality of life of diabetic patients.

At first, they named the hypoglycemic substance of pancreatic extract insulin. Later, mcleod discovered that in 1909, the Belgian doctor Mel had named this hypothetical substance at that time (see the picture above), so he followed Mel's name and renamed it insulin. 1922 on may 3, they published their research results again at the American physiological society in Washington. They were treated completely differently from last time. They won applause from the audience and were hailed as the greatest achievements of contemporary medicine.

After the invention of insulin, they met another problem. Wave after wave 1 type diabetic patients poured into Toronto, and the output extracted by Klipp laboratory could not meet the demand. Later, they cooperated with Lilly Company in Indiana to produce insulin on a large scale in a commercial way. They also cooperated with Denmark and Britain to produce insulin with the consent of the patent owner, the University of Toronto. By June 1923, insulin can be used in North America and Europe. This year, the Nobel Committee quickly approved Banting and mcleod as this year's medical prize winners. Wanzin announced that they would share the prize money with Best, and mcleod would also share it with Klip. The relative advantages, contributions and winners of these four people in the research of insulin invention were also debated at that time. Later generations generally believe that this research is a team work, and the research motivation comes from Wanjin, with the help of Best's work in the laboratory. Mcleod is the host of the whole study; Klip has made a great breakthrough in the method of extracting insulin, and these four people deserve the Nobel Prize in Medicine. The University of Toronto has also made great contributions in providing research funds, equipment and experimental animals. After insulin was discovered, the research group was dissolved. Mcleod was still the head of the Department of Physiology at the University of Toronto and died in 1935. Banting, director of the research department of the university, died in a plane crash in 194 1 year. Best later became a professor of physiology to continue diabetes research, and actively participated in the establishment and development of the American Diabetes Association, and died on 1978. Klip moved to Edmonton University in Alberta, and made great contributions to the later discovery of parathyroid hormone. He died in 1965. Thompson, the first diabetic who received insulin therapy, died in 1935 and lived for 13 years, which would never have happened before the invention of insulin. 1922 At least two of the earliest diabetic patients who received insulin treatment in Toronto died later than the four insulin inventors, and one of them died in 1993 at the age of 76.