Science entered the experimental period in the nineteenth century, a century that was an important period in the development of most medical sciences. Oskar Minkowiski and Josef Von Mering wanted to know if the pancreas was a necessary organ for sustaining life. They removed the pancreas of a dog in 1889, and the dog ate more, drank more, urinated more, had elevated blood glucose, and urinated glucose, which made it clear that the pancreas was involved in diabetes. The pancreas may secrete a glucose-lowering substance, but where this glucose-lowering substance originates from the pancreas has always been a mystery. A few years ago, there was a doctoral student named Paul Langerhans in Berlin, Germany, who found that there were a mass of special cells in the pancreas, which could be separated from the pancreatic exocrine cells or the pancreatic ducts, and what was the function of these cells? Langerhans did not state further, until 1893 Laguesse (Edouard Laguesse), only these cells named Langerhans islets, think and pancreatic endocrine related. 1909 a Belgian physician Meyer (Jean de Meyer) that Langerhans islets may be the secretion of hypoglycemic hormone place, and will be such a hormone named Insulin ( Insuline.)
Early insulin extraction
Because the pancreas is generally believed to contain glucose-lowering substances, some scholars in the early twentieth century devoted themselves to the study of pancreatic extraction of glucose-lowering substances. A Berlin physician named Zuelzer (George Zuelzer), he found that some pancreatic extracts can make the removal of the pancreas after the dog's urinary glucose excretion is reduced, acidosis can also be improved. Some of these extracts can even cause low blood sugar in dogs, and one of his extracts has been patented in the United States (called Acomatol). In order to make his research more substantial, Shang delayed a few years, until 1907 to officially publish the research report. Although his pancreatic extract was used in eight diabetic patients, the side effects were too great to be overcome and he had to end the clinical trials.
Nicolas Paulesco, a physician and professor of physiology in the Romanian capital of Bucharest, also succeeded in extracting hypoglycemic substances from the pancreas of dogs and cattle. The first time the extract was injected into a dog, the dog died of hypoglycemia, and he named the extract Pancreine. Due to the outbreak of World War I, his research was not published until 1921, and Pancreine could not be used in the clinic because of fever and other serious side effects.
Israel Kleiner of Rockefeller University in the United States in 1919 documented in a very organized manner a series of changes in blood glucose in animals after administration of pancreatic extracts, but unfortunately he had to terminate his work in this area because of a change of job, lack of equipment in the new premises, and the absence of an animal research laboratory.
Successful insulin extraction
Toronto, Canada, Banting physician (Frederick Grant Banting) is an enthusiastic surgeon of new inventions. December 30, 1920, late at night at 2 o'clock, he got an inspiration, so in the notebook recorded a simple paragraph: "Diabetes mellitus, the pancreatic ducts of the dog tied to the pancreas, so that the pancreatic gland exocrine gland degradation, need to make the dog survive. The dog's pancreatic duct was tied down, causing the exocrine glands of the pancreas to degenerate, and the dog had to be kept alive, and then an attempt was made to isolate the endocrine secretions to alleviate the diabetes. Dr. Bunting, a skilled surgeon but inexperienced in diabetes and related research, consulted J.J.R. Macleod, then a respected professor of physiology at the University of Toronto, who in the summer of 1921 agreed to provide him with a laboratory, experimental animals (dogs), and a student research assistant, Charles H Best. The earliest studies of Banting and Best were conducted in the early days. Banting and Best's earliest research began with organ transplantation, in which they tied the pancreatic ducts to isolate the atrophied pancreas and transplanted it into diabetic dogs from which the pancreas had been removed, but they soon abandoned this method when McLeod suggested that they cool extracts of the atrophied pancreas and then inject them directly into the dogs. After many trials Banting and Best found that the hypoglycemic effect of the whole pancreas extract was comparable to that of the atrophied pancreas extract after tying the pancreatic ducts, so the pancreas was extracted directly from the pancreas without tying the ducts first. At Dr. Banting's request, McLeod invited James B Collip, a scholar with considerable biochemistry expertise, to join the research team in December. Banting and Best gave an oral presentation to the American Physiological Society on December 30, 1921, which was later published as a paper in J Laboratory & Clinical Medicine, where their findings were met with much skepticism and other side effects, such as fever, could not be resolved. The general consensus was that the results were no better than those of the previous studies by Chu, Bausch & Lomb, and Claire.
Clipp joined the team and worked to improve the extraction method and discovered that injections of pancreatic extracts increased liver glycogen stores and eliminated urinary ketones, and on January 1, 1922, they injected the extracts for the first time in humans. Leonard Thompson (then 14 years old, with type 1 diabetes, hospitalized in the Toronto General Hospital, for the frequent death of patients, Thompson received extract injections, but the symptoms did not improve, and in the injection site of aseptic abscess. Collip continued to improve the extraction method, a few days later, that is, January 23 Tompkinson received another injection, the result is that blood sugar returned to normal, urine sugar and urine ketones have disappeared. It was this simple clinical trial that opened a new era in insulin therapy for diabetes, saving the lives of countless type 1 diabetics and dramatically improving the quality of life for diabetics.
The earliest they named the hypoglycemic substance of pancreatic extract Isletin, later McLeod found that in 1909, the Belgian physician Meier had already named the substance which was only hypothetical at that time (see the aforementioned), so they followed Meier's name and changed the name to Insulin (insulin). May 3, 1922, they were in Washington, D.C., at the American Physiological Society to present the results of their research again. On May 3, 1922, they presented their research again at the American Physiological Society in Washington, D.C. They were treated very differently from the last time, receiving a standing ovation from the audience and hailed as the greatest achievement of contemporary medicine.
After the invention of insulin, they encountered another nuisance. Wave after wave of type 1 diabetics were flooding into Toronto, and the Collips Laboratory Extraction Method, the production could not keep up with the demand. They later partnered with Eli Lilly Co. of Indiana to produce large quantities commercially, and also with the consent of the University of Toronto, the owner of the patent, to produce insulin in cooperation with Denmark and England, and by October 1923 insulin was available in North America and Europe. That year the Nobel Prize Committee was also quick to recognize Banting and McLeod as the winners of that year's medical prize. Banting announced that their prizes would be divided equally between Best and McLeod between Collip. The relative merits, contributions, and recipients of the prize for these four men's research into the invention of insulin were also debated at the time. It is generally recognized that the research was a team effort, with the motivation for the research originating from Banting and helped by Best's work in the laboratory; McLeod was the facilitator of the entire research; Collip obtained a major breakthrough in the method of insulin extraction, and the four should be **** officially awarded the Nobel Prize for Medicine; and the University of Toronto also deserves credit for the funding of the research, the equipment, and the provision of experimental animals. After the discovery of insulin, the team split up. McLeod remained head of the Department of Physiology at the University of Toronto until his death in 1935. Banting died in a plane crash in 1941 while serving as director of research at the university. Best became a professor of physiology and continued diabetes research and was active in the establishment and development of the American Diabetes Association before his death in 1978. Collip moved to Edmonton University in Alberta and was instrumental in the discovery of the parathyroid hormone, dying in 1965. The first insulin-treated diabetic, Thompson, died in 1935, having lived an extra 13 years, something that would never have happened before the invention of insulin. At least two of the first insulin-treated diabetics in Toronto in 1922 died later than the four insulin inventors, and one of them died in 1993 at the age of 76.