To solve the problems of mass production and impurities, they worked with Eli Lilly and Co. in the United States to isolate enough insulin from animal pancreas obtained from slaughterhouses to provide it to diabetics worldwide. In less than two years, the insulin was in use in hospitals around the world with unprecedented success. In October 1923, the Caroline Institute in Sweden decided to award the Nobel Prize in Physiology and Medicine to Banting and McLeod. When Banting learned of the decision, he immediately announced that he would share his prize with Best; later, McLeod announced that he would share his prize with another biochemist, James Collip (1892-1965), who had been involved in the research.
Doctors and researchers have a lot of experience in the field of physiology and medicine, and they have a lot of experience in the field of biochemistry.
Over the years, anyone who has studied physiology or endocrinology has probably heard or read that insulin was discovered by Banting and Best, and those who know a little more about it have been told that Banting succeeded because of an idea he came up with from reading the journals: to ligate the pancreatic ducts of dogs, so that the exocrine glands that secrete digestive juices would atrophy, and then take the pancreas out and extract it, thus avoiding the need for the active substance (which is also known as the pancreatic juice) to be removed. The active substance (i.e., insulin) is broken down by digestive enzymes. Others would say that McLeod took neither credit nor blame for the discovery of insulin, and that he simply took advantage of a ready-made bargain. As for who Collip was and what he contributed, no one outside the endocrinology community probably knows.
This case in the history of science has been deliberately hidden for more than half a century for various reasons. It was not until 1982 that Michael Bliss, a professor of history at the University of Toronto, wrote The Discovery of Insulin (1982, University of Toronto, University of Toronto, 1982) from many historical documents (including Banting's original lab notes, declassified documents from the Nobel Prize Committee, etc.) and interviews with witnesses (mostly 70- and 80-year-olds). The Discovery of Insulin, 1982, University of Chicago Press), which roughly restored the truth of the events that happened between 1921 and 1923. The saying that "real life is better than a novelist's creation" has been reaffirmed here.
From the time Banting first formally reported his preliminary findings at the annual meeting of the American Physiological Society in December 1921, less than two years later, he was recognized with the Nobel Prize, which is unprecedented and unmatched; not to mention the fact that when he was awarded the prize, insulin was formally tested in clinical trials for only a year, which made it difficult to assess its long-term benefits. But what seems impossible today did happen, and the main reason was the severity of the diabetes.
Diabetes is a long-standing human disease, and the problem is that the body cannot utilize glucose, the most important source of energy, so there is a large amount of glucose buildup in the bloodstream, which can cause vascular disease and the growth of germs; and at the same time, there is an excessive loss of glucose from the urine, which can take away a great deal of water and cause the patient to be hungry and thirsty. Even if the patient continues to eat and drink, he or she still loses weight (protein and fat are broken down to make more glucose), and an increase in diet will only make the situation worse, which is why Traditional Chinese Medicine (TCM) refers to this disease as "thirst-quenching syndrome". Under prolonged "starvation", the body's tissues begin to utilize ketone bodies; large amounts of ketone bodies produced from fats and amino acids are acidic and cause acidosis in the patient.
Before the discovery of insulin, the common method of diabetes control was fasting. On a strict diet of less than 1,000 calories per day, with little or no carbohydrates, diabetics, who were already thin, were reduced to a state of starvation. These people can weigh as little as 20 kilograms and lie in bed all day long without even the strength to lift their heads. Even if they don't die of coma caused by acidosis, they will sooner or later die of starvation. This is the first time that we have seen the world's first-ever Chinese food market, and it is the first time that we have seen the world's first-ever Chinese food market.
In the industrialized world of the 1920s, the prevalence of diabetes ranged from 0.5% to 2% (sadly, this figure increased after the discovery of insulin), and included important people and their families, such as the daughter of the Secretary of State, the son of the vice president of Kodak, and George Minot (1885-1951), the Harvard doctor who won the 1934 Nobel Prize for his discovery of the cure for pernicious anemia. George Minot (1885-1950), a Harvard physician who won the 1934 Nobel Prize for his discovery of a cure for pernicious anemia.
Who actually discovered insulin? Is the conventional wisdom wrong? We have to start with Banting.
In 1917, Banting graduated from the University of Toronto Medical School. At the outbreak of the First World War, Banting did not attend any classes in his final year, and took only five pages of notes throughout the year (he later admitted that his medical education was incomplete), and was drafted into the army as a medical officer, and went to the front in France to participate in the Battle of Cambrai (Battle of Cambrai, the first time tanks were successfully used on the battlefield), and was honorably discharged because of his injuries. Unable to find a job in a major hospital, Banting was forced to practise in London, a small city 180 kilometers away from Toronto.
Business was slow, so Banting found part-time work at the local medical school at the University of Western Ontario, where his knowledge of diabetes was gained through preparation for lectures. In October 1920, he read a pathology report describing a patient whose pancreatic duct had been blocked by a stone and whose exocrine glands, which secrete digestive enzymes in the pancreas, had atrophied, but the islet cells had survived. So Banting thought he could surgically ligate the pancreatic ducts of dogs to simulate stone obstruction; after the digestive glands atrophied, he might be able to isolate the unknown hypoglycemic substances in the islets.
Since Oskar Minkowski discovered the link between the pancreas and diabetes in 1889, there have been many attempts to isolate the mysterious endocrine substances in the pancreas, and there have been reports that pancreatic extracts have hypoglycemic effects; however, either they are not effective enough, or the side effects are so great that they have not been recognized by their peers. The results of Banting and Best's hard work in the summer of 1921 did not surpass those of their predecessors; if not for the help of McLeod and Collip, they would have failed to taste the fruits of victory.
Throughout his life, Banting believed that his bright idea was the source of his success, and through his advocacy and second-hand reporting, the story spread. But the truth is that ligation of the pancreatic duct is completely unnecessary. The digestive enzymes secreted by the pancreas are in a non-activated state until they enter the digestive tract and do not break down insulin; furthermore, crushing the pancreas at low temperatures and extracting the pancreas with alcohol removes the effects of the digestive enzymes (this is not an afterthought, as has been pointed out in the past). So here's the paradox: Banting's success was due to his ignorance of the research.
McLeod, a Scot with a full research credentials in England, Germany, and throughout the United States, was then president of the American Physiological Society, specializing in the physiology of carbohydrate metabolism. McLeod was a competent researcher, familiar with the medical literature and more adept at integrating existing physiological knowledge, and he was also a prolific author. When Banting, who had no research experience, came to him with a premature idea, his instinctive reaction was to ask why Banting, a nobody, would succeed when so many others had already tried and failed. Maybe he thought that Banting's idea hadn't been done before, so he might as well give it a try; maybe he thought that Banting was at least a surgeon, so he probably wouldn't have any problem operating on a dog; moreover, McLeod had to go back to his home country of Scotland to take a vacation in the summer, so it would be a good idea to have someone else to do the work in the lab. So he agreed to give Banting a try, and asked Best to help; history was thus made.
In mid-May 1921, Banting performed his first pancreatectomy on a dog; he had probably never done anything like it before, so McLeod was there to help. McLeod only left Toronto in mid-June, and rumors that he was not involved in the experiment at all are incorrect. Due to technical problems, the heat and the poor conditions in the animal room, the mortality rate was high: fourteen out of nineteen animals died (antibiotics were not yet available either). Of the five dogs that survived the ligation of the pancreatic ducts, only two showed atrophy of the pancreas, while the rest were ineffective due to poor ligation; however, they were extracted and injected, and a lowering of blood glucose was observed.
From a purely research point of view, Banting's and Best's results were crude; their first two papers contained many errors. Banting and Best's initial results would not have been credible if McLeod had not incorporated many of the experimental results of the physiological parameters, and had not invited biochemist Collip to join in the research and improve the extraction and purification methods. As the saying goes, "Success has many fathers, failure is only an orphan". The discoverer of insulin was a controversial figure from the beginning, and there was also solidarity with many of the forgotten researchers who had previously worked on the subject. Throughout his life, Banting believed that McLeod had robbed him and Best of their results, and bad-mouthed them. In 1928, McLeod finally left Toronto to return home to teach at the University of Aberdeen, where he died seven years later at the age of fifty-nine.
Because Banting was the first Canadian to receive the Nobel Prize, he received unusually favorable treatment from the Canadian government, not only a tenured position as a research professor at the University of Toronto, but also an institute named after him and Bester. Banting's achievements in scientific research were limited, but his personality and life were dramatic. During World War II, Banting served as chairman of wartime medical research and was based in England. In 1941, he was killed in a plane crash on his way back to England at the age of 50. The authors of The Discovery of Insulin have written a separate biography of Banting (Banting: A Biography, 1984), which gives more coverage to Banting's life.
The other two **** co-discoverers of insulin, Best and Collip, were not recognized by the Nobel Prize, but they went on to do much better, and lived to a ripe old age. It seems that the "Nobel Prize is a researcher's grave" is not without some truth.
According to general accounts, it is said that Best, who helped Banting with his experiments, was a medical student, which is not true. Best had just received his bachelor's degree in physiology from the University of Toronto and was accepted into graduate school. He received his master's degree in 1922 before entering medical school, where he graduated in 1925 with first class honors.
With the title of "co-discoverer of insulin," Best accepted the advice of Henry Dale (1975-1968, Nobel Prize in Physiology and Medicine, 1936), a leading British physiologist at the time, and went to Dale's laboratory to receive a full research training and to obtain his Ph. Ph. When McLeod left the University of Toronto in 1928, Best was the logical replacement, becoming the youngest and most promising physiologist of his time. Bester lived up to his reputation and made important contributions to the role of insulin and the development of anticoagulants. His textbook on physiology, "Best and Taylor's Physiological Basis of Medical Practice," has also been consistently issued in a new edition (13th ed. 1999, edited by a different author), and thus it is still being heard of by a new generation of physiologists.
The last person to join the work was Collip, a professor in the Department of Biochemistry at the University of Alberta, Canada, who was on a year-long sabbatical at the University of Toronto. He had a great interest in the fledgling field of endocrinology and therefore followed closely the pancreatic extraction work of Banting and Best. When Banting hit a bottleneck in purifying insulin, he invited Collip to join him and help. Although Collip later politely remarked that he had done what any biochemist would have done, anyone who knows the complexity of protein chemistry and the paucity of methods available eighty years ago can appreciate the difficulty of his work. Collip later made important contributions to the isolation of many endocrine hormones. He also served with great distinction as head of the Department of Biochemistry at McGill University and as Dean of the Faculty of Medicine at the University of Western Ontario.
Although the discovery of insulin has saved the lives of millions of people with diabetes, it is only a cure for the symptoms, not the root cause, and those who lack insulin will have to rely on insulin injections throughout their lives to keep their blood glucose under control and avoid complications. What is even more troublesome is that there is more than one type of diabetes, there are more so-called adult type (type 2) diabetes patients, the body does not lack of insulin, but due to overweight, little movement, and over-eating, resulting in a decline in the body's tissue response to insulin, and unable to effectively utilize excess energy before the onset of the disease. Especially in today's middle-aged people, most of them were quite slim when they were young, and the number of fat cells in their body is limited (the number of fat cells no longer increases after adulthood); but in recent years, they eat too well, resulting in every fat cell is full, and they are unable to absorb more energy, and thus they are prone to develop the symptoms of diabetes. For this kind of patients who are more in number, supplemental insulin will be of little use, exercise, weight loss, pay attention to diet is the remedy.
Although the discovery of insulin has a history of eighty years, insulin can be regarded as one of the most difficult to understand the hormone, the role of the diverse, complex mechanisms, so far has not been fully unraveled. The insulin isolated by Banting and others was only a crude product, and the real purification and structural decision was not completed until 1955 by Frederick Sanger of the United Kingdom (1918- ), who was awarded the 1958 Nobel Prize in Chemistry.
Another indirect winner of the Nobel Prize for insulin research was Rosalyn Yalow (1921- ), who won the prize for physiology and medicine in 1977. Yalow and his colleague Solomon Berson (1918-1972) found that the blood of diabetic patients who had been injecting insulin for a long time contained a certain kind of globulin, which could bind to insulin; after analyzing the globulin, it was found that the globulin was an antibody against insulin. Since insulin is present in the body itself, the production of antibodies to insulin was incredible, and their earliest (1955) paper reporting this discovery was rejected by the Journal of Clinical Investigation. Yalow kept the rejection letter from that year, and twenty-two years later, when she won a prize, she took it out and published it in Science. There are two lessons to be learned from Yalow's story: one, to win a Nobel Prize, you have to live a little longer, like Berson missed out; and two, don't offend women.
The problem with the above is that the insulin given to patients back then came from animal pancreases in slaughterhouses. Although animal insulin also works in humans, there are still a few differences in its amino acid composition; immune cells produce special antibodies in response to this difference. This is no longer a problem with genetically engineered human insulin. By utilizing this antigen-antibody specific reaction, coupled with the use of radioactive elements as a tracking agent, Yalow and Berson developed the "radioimmunoassay" (radioimmunoassay), which is capable of determining trace amounts of hormones in the blood, as well as any antibody-producing substances, and has revolutionized the face of endocrinology.
Thus, history is often more subtle and recurrent than one can imagine, as seen in the story of insulin.
Thus, the story of insulin is one of the most obscure and recurrent in history.