Discovering/history of insulin doctor Banting broke

 On January 11, 1922, the air in Toronto, Canada was cold and clear. Thomson, a 14-year-old boy, curled up in a chair in front of the window, enjoying the warm winter sun. A thick blanket wrapped the boy's body tightly, and a corner of the blanket was hanging loosely on the pinewood floor.

It had just snowed in the New Year, and the scenery outside the window was beautiful. But Thomson couldn't go downstairs to play like other kids. He weighed in last week, and he now weighs less than 30 kilograms. Now, he spends most of his time sleeping, and when he is at his best, he sits in front of the window and looks at the scenery. Little Thomson felt that recently his mother was spending more and more time with him, and he was sensitively aware that he might be dying.

Thomson's mother was standing quietly behind the chair. She looked at the child with the calmest eyes, but her mood was extremely complicated. Just a week ago, four scientists from the University of Toronto approached her, saying that they had developed a new drug that could cure little Thomson’s disease. This is of course a great thing for young Thomson, but what makes her entangled is that this medicine has never been tried on anyone. If she agrees to receive treatment, Jr. Thomson will be the first patient to use the drug. She finally agreed to the treatment, but she did not convey the confidence of the scientists to Jr. Thomson. This poor child has already experienced too much pain, and she does not want her child to be disappointed again in the last days of her life. In the afternoon at the Toronto hospital, Jr. Thomson received an injection. However, the results of the treatment apparently hit the scientists in the face, and Thomson's disease showed no signs of improvement. A few hours later, an abscess began to appear at the injection site where Jr. Thomson received the injection. After the scientists tested little Thomson's blood sugar levels several times, they had to admit that the treatment had failed. Looking at the little Thomson who was sleeping in the chair, his mother couldn't help being sad anymore and wept helplessly. Little Thomson’s disease is actually diabetes that everyone has heard of. You may not imagine that just 100 years ago, diabetes was not a chronic disease that could be controlled and treated. Diabetes at that time can easily take the lives of patients. Today I will tell you the tortuous story of the struggle between humans and diabetes. The ancient history of diabetes The prevalence of diabetes is extremely high, about 1 in 11 people is a diabetic. People suffering from diabetes will be prone to thirst, eating larger amounts of food, but gradually losing weight. Because the symptoms are very special, the ancients were able to accurately identify diabetes long ago. In a burial complex of ancient Egyptian nobles more than 3,500 years ago, archaeologists identified the identity of Pharaoh Yahemos I. Next to his tomb, people found one of the oldest medical books to date. After deciphering the text recorded above, the archaeologists were surprised to find that it actually recorded a disease called "polyuria". One of the symptoms of the patient is that the amount of water and urine is very large. This is the oldest medical record of diabetes. Although the record of diabetes in my country is not as early as in Egypt, it has a more thorough understanding. There is a record of diabetes in the "Huang Di Nei Jing" more than 2000 years ago. The name of the disease alone clearly describes the two characteristics of diabetic patients' weight loss and thirst. In the early years of the Tang Dynasty, the famous physician Zhen Liyan left a record of sweet urine in diabetic patients in his book "Ancient and Modern Records of Prescriptions". However, limited by the conditions at the time, the ancient medical scientists finally stopped at the diagnosis and description of diabetes. If you do not understand the cause of diabetes from a physiological perspective, there is no way to provide effective treatment for patients. It was not until a few accidental discoveries at the end of the 19th century that the curtain of human struggle with diabetes was opened. Dogs can also get diabetes The first unexpected discovery came from a pasture called goat bean. American herders have found that feeding goat beans to sheep can significantly increase the milk production of goats. But if you eat too much, goats will suffer from hypoglycemia or even death. Can cause hypoglycemia, isn't this a good medicine for diabetes? This immediately attracted the attention of scientists. Further research found that it is the guanidine compound caprine in goat beans that plays the role of lowering blood sugar, but caprine is too toxic, and there is still a long way to go before clinical application. But this gives scientists a research direction, that is, as long as a safe guanidine compound is found, it is possible to treat diabetes.


Another unexpected discovery came from the German physiologist Oskar Minkowski. When dissecting the experimental animals, he noticed that the pancreas, located between the stomach and the small intestine, was connected to the small intestine by a thin tube. According to the general knowledge at the time, the pancreas provided a certain digestive function. However, this vague definition of a certain digestive function angered the rigorous Minkowski. He believes that it is necessary to thoroughly understand the specific functions of the pancreas. Minkowski’s idea was to find a dog, remove its pancreas, and see what happens. This idea was quite bold at the time, because the mainstream view at the time believed that every major organ has an irreplaceable function. If the dog’s pancreas is removed, the dog will not survive. But Minkowski doesn't think so. If people don't know the function of the pancreas, how can they say that a dog with a pancreas removed will die? So, he tried to persuade his old partner Merlin to help him with this operation. Sure enough, the operation was very successful. Not only did the dog with the pancreas survived, it seemed to show better appetite. Minkowski and Merlin observed together for several days, but they didn't find anything abnormal in the dog whose pancreas was removed. Just when they were confused, the experiment assistant complained that the well-trained puppy always urinates everywhere, and its urine is especially fond of flies. This casual complaint immediately inspired Merlin. He wondered, would the removal of the pancreas change the composition of the dog's urine? They immediately measured the puppy's urine composition and found that the sugar content in it was significantly higher than that of healthy dogs. After another few days, the puppies' symptoms of irritability, easy thirst, increased urine output, and weight loss became more and more obvious, which were exactly the same as those of diabetic patients. This result made Minkowski ecstatic. He never expected that the removal of the pancreas would make the dog suffer from diabetes. The mystery of the cause of diabetes, which has plagued humans for thousands of years, has been solved by mistake .

Picture: Oscar Minkowski Insulin is ready to come out After confirming the correlation between the pancreas and diabetes, research on diabetes quickly became a hot topic. But the biggest challenge of this research is that scientists have not found the difference between the pancreas of healthy people and diabetic people. In 1901, the American doctor Eugene Opie accidentally discovered during anatomy training that there were some cell clusters of irregular size and shape in the pancreas. These cell clusters were like small islands scattered in the central part of the pancreas. In the cell. Opie named them pancreatic islet cells. In the pancreas of diabetic people, most of the tissue is exactly the same as that of normal people, and only the pancreatic islet cells show a shrinking morphology. Opie guessed that these shrinking pancreatic islet cells should be the culprit for diabetes. Maybe they can secrete something similar to digestive juice, which affects the regulation of blood sugar concentration.

Picture: Pancreatic Islet Cells Opie's discovery immediately put the troubled diabetes research on the right track. As long as you find this substance that can regulate blood sugar, it is possible to treat diabetes, which was once incurable. Scientists are eager to find this substance as soon as possible. They even named this substance early, called "insulin." The work of extracting insulin seems simple, but the progress is not so smooth. German doctor George Zurzer tried to use the extract of bovine pancreas to treat critically ill diabetic patients, but the effect was not obvious. Scientists at the time believed that this was just a problem of compound extraction. The reason for the lack of obvious effect was the lack of purity. It only took 3-5 years to finally make a breakthrough. But 10 years later, the issue of insulin extraction still has not progressed at all. Scientists speculate that this may be because the pancreas secretes other digestive juices while secreting insulin. When these digestive juices are mixed with insulin, insulin will be degraded. This speculation was later confirmed by modern medicine that the substance that affected the extraction of insulin did exist, that is, trypsin secreted by the pancreas. In fact, it is not the purification technology that has stuck many scientists, but the lack of understanding of the pathological mechanism of diabetes. Science and technology are always growing alternately in mutual support. A few years later, a young doctor's new understanding of the physiology of the pancreas once again broke the deadlock. The Break of the Young Doctor On the evening of October 30, 1920, the weather was clear and the moon was clear. Part-time teacher Frederick Banting stayed in his small clinic and did not go home. He had to prepare a lecture on diabetes for his course overnight. During the preparation of the lecture, an interesting case report attracted him: a patient's pancreatic duct was blocked by a stone, causing the pancreatic alveolar cells that secrete digestive enzymes to shrink. However, the islet cells in the pancreas responsible for regulating blood sugar were unharmed.

Picture: Frederick Banting This case gave Banting an inspiration. He thought, if you imitate the situation in the case, surgically ligate the dog's pancreatic duct, wait for the pancreatic alveolar cells that secrete digestive enzymes to shrink, and then extract insulin, will it be successful? Just do it. Thinking of this, Banting didn't even have the heart to write the handout. He quit his job as a part-time teacher, closed the small clinic on which he lived, and returned to his alma mater, the University of Toronto, in a ruined manner. He hoped that Professor McLeod, an authority on diabetes, would support his research.


Banting excitedly said to Professor McLeod: "I thought of a way to purify insulin. Can you give me a few dogs and a laboratory? I will definitely be able to achieve results!" But Professor McLeod was not at all impressed by Banting's passion. On the contrary, he felt that Banting's ideas were too crazy and it was better to give up as soon as possible. Unlike Banting, who is unknown, Professor McLeod is a renowned diabetes expert. He understands the failures experienced by his colleagues in this industry, and he will no longer be excited by an idea. Banting of course also understands what the professor means. After all, those academic experts and well-known doctors have been working hard for many years to extract insulin, and they have tried almost any method. How can they leave the opportunity to him, a semi-amateur. Where's the lad? However, Banting did not give up. If Banting has any qualities that can affect his future, it should be courage and persistence. Banting has always been a man who has made progress since he was a child, and this time is no exception. In the months that followed, Banting visited McLeod several times, repeatedly telling him about his experimental ideas. In May 1921, Professor McLeod prepared to leave the school and return to his home in Scotland for a holiday. His laboratory was idle during this time. I don't know if he was moved by Banting's obsession, or he became interested in Banting's experimental design, and even agreed to Banting's request. He assigned 10 dogs to Banting, allowed him to use his own laboratory, and sent a 21-year-old young assistant Charles Best to help Banting. For Banting, this happiness came too suddenly.

Banting's experiment requires two types of surgery. One is to ligate the pancreatic duct for the dog, wait for the dog's pancreatic vesicles to shrink, and then take out the pancreas as the raw material for extracting insulin. The other is to take the pancreas for the dogs and turn them into diabetic dogs. The reason why a dog with diabetes is needed is because the insulin concentration in the extract must be tested at any time during the insulin extraction process. The only way at that time was to experiment directly on diabetic dogs, and judge the effect of purification based on the treatment level of the extract. Banting and Best are both true novices at the surgical level. The pancreatic duct ligation operation went smoothly, but when it came time to remove the pancreas from the dog, they couldn't handle it. 10 puppies died on the operating table in a short period of time. There was no way, they had to buy dogs out of their pockets to continue the experiment. After the sacrifice of 91 puppies, the two people finally observed a significant hypoglycemic effect on experimental dog No. 92.

When Professor McLeod came back from vacation, he was a little surprised to see that the two young men had actually made achievements. But in the eyes of MacLeod, who is proficient in surgery, in order to complete such a simple experiment, there are so many puppies sacrificed on the operating table, which is really dumbfounding. With the addition of McLeod, this three-person team finally looked less amateurish. They first replaced the puppies with cattle pancreas purchased from the slaughterhouse, and then found a new method of soaking and purifying acidified alcohol, and the project began to progress rapidly. In order to mention more pure insulin, McLeod also dragged James Colip, a young biochemist who just came to Toronto to study and specializes in protein extraction, to join the research team, so that the team finally had some top-notch. What the research team looks like. First patient In January 1922, the four-person team finally faced a real challenge after numerous successful animal experiments. Professor McLeod contacted Leonardo Thomson, a 14-year-old patient with severe diabetes. On January 11th, Thomson will become the first clinical patient with purified insulin. This is the story we tell at the beginning of this article. After the first injection, the boy Thomson's condition did not improve significantly, on the contrary, an abscess appeared at the injection site. Fortunately, no more serious adverse reactions occurred in the little boy. Although these insulins have been repeatedly purified, there are still too many impurities for clinical injection. At this critical juncture, Colip, who specializes in protein extraction, proposed that he could perform another round of purification on the extract and try again. January 23, 1922, this is a day worth remembering forever. Thomson received insulin therapy for the second time. This time a miracle happened. The little boy's blood sugar dropped to a normal level rapidly within a few hours, and the symptoms of diabetes gradually disappeared. A few days later, Thomson, who was dying, regained his vigor and vitality, which meant that the era when diabetes equated with death was gone forever! In May 1922, Banting's four-person team announced the results of clinical trials. As soon as the result came out, the news immediately shocked the world. All the researchers admired their achievements. Countless people sent their sick family members to the Toronto hospital just to wait for the life-saving shot.

At the same time, the Irish chemists Werner and Bell on the opposite side of the Atlantic also completed an equally important research result. They synthesized a new kind of guanidine compound in the laboratory, which later became famous all over the world. The hypoglycemic drug metformin. However, under the background of the successful purification of insulin, the advent of metformin did not cause waves in the diabetes medical field. All the spotlights were on the Banting team who completed the purification of insulin, which left metformin in the cold for 20 years. as long as.


In 1923, Banting and McLeod took the world's expectations to the laurels soapbox. it absolutely was solely a year since they initial discharged the results of clinical treatment of hypoglycemic agent. several scientists usually have to be compelled to watch for decades so as to get on the laurels soapbox. the explanation why the Banting team will win the prize at the speed of sunshine is enough to clarify the importance of hypoglycemic agent to the globe. The perplexity of natural hypoglycemic agent One of the vital tasks for the Banting team when winning the award is to determine a way to allot the pitiful quantity of hypoglycemic agent. Banting definitely hopes to fulfill everyone's needs, however subject to hypoglycemic agent production, some individuals area unit destined to fail. The potency of extracting hypoglycemic agent from animal duct gland is very low. The hypoglycemic agent which will be obtained by slaughtering a pig is just enough for a diabetic patient to use it for seven days, and each diabetic patient should take the medication forever. so as to extract additional hypoglycemic agent, the duct gland of eutherian mammal has turned from a useless material into a very important resource that's onerous to seek out nightlong. In addition, though animal hypoglycemic agent will treat people’s polygenic disease, its structure is completely different from natural human hypoglycemic agent in any case. These variations area unit seemingly to be recognized by the human’s sensitive system and trigger an exact degree of immunologic response. this can be AN inevitable facet impact of animal hypoglycemic agent. to supply human hypoglycemic agent while not facet effects, there's solely chemical synthesis. Synthetic hypoglycemic agent In 1955, British chemist Sanger completed the sequencing of all fifty one amino acids of bovine hypoglycemic agent. you'll raise, why will Sanger live bovine hypoglycemic agent rather than human insulin? the solution is additionally terribly easy. this can be simply because bovine hypoglycemic agent is simpler to get and can not have an effect on the progress of the analysis. however this doesn't matter. Sanger's greatest contribution is to excellent the strategy of hypoglycemic agent macromolecule sequencing. together with his work, it's become abundant easier to additional complete the aminoalkanoic acid sequencing of human hypoglycemic agent. Sanger's achievements additionally helped him win the 1958 laurels in Chemistry.

In the same year that Sanger won the laurels, the project of artificial bovine hypoglycemic agent junction rectifier by the Shanghai Institute of organic chemistry of the Chinese Academy of Sciences was launched. when seven years of toil, Chinese scientists finally took the lead in finishing the unreal synthesis of bovine hypoglycemic agent in 1965. this can be additionally the world's initial artificial synthesis of macromolecule. the explanation why Chinese scientists favor to synthesize bovine hypoglycemic agent is that the same as that of Sanger. this can be solely as a result of solely the aminoalkanoic acid sequence of bovine hypoglycemic agent was famous. The artificial synthesis of bovine hypoglycemic agent undoubtedly proves that humans will create any quite natural macromolecule within the laboratory. From the angle of life sciences, this can be beyond any doubt a landmark initiative. However, what Chinese scientists failed to recognize at the time was that from the angle of polygenic disease treatment, this wasn't an accurate research project route. In a laboratory atmosphere, if you would like to "connect" a replacement aminoalkanoic acid to AN existing aminoalkanoic acid sequence, the chance of success is just some thousandths. hypoglycemic agent could be a macromolecule that contains fifty one amino acids. If every aminoalkanoic acid is correctly connected, the synthesis potency are very low. it's virtually not possible to induce such inefficient technology from the laboratory into the manufacturing plant. After recognizing the constraints of chemical synthesis, scientists began to do to seek out answers in nature. Since hypoglycemic agent itself is synthesized in duct gland isle cells, will microorganism replace duct gland isle cells to synthesize giant amounts of insulin? the solution is affirmative. In 1972, 2 young biologists-Stanley Cohen of Stanford University and Victor Herbert Boyle of the University of Calif., urban center collided at an educational conference dinner. They completed that mistreatment restriction enzymes that area unit wide gift in microorganism, it's attainable to chop out polymer sequences that individuals have designed earlier. once this microorganism divides, it will turn out the macromolecule product we wish. This method of mistreatment microorganism to supply macromolecule is biotechnology.

Picture: Victor Herbert Boyle (left), Stanley Cohen (right) In 1976, Henry M. Robert actress, AN capitalist in geographical area with a keen sense of smell, found Boyle when realizing the enticing prospects of biotechnology. when they met, it hit it off and that they each resigned and collectively supported the far-famed Genentech Biotechnology Company. simply 2 years later, Genentech declared the production of human hypoglycemic agent. The world's initial genetically built drug was born! Type I add sort II After biotechnology solved the matter of production of human hypoglycemic agent, human hypoglycemic agent has slowly born to the civilian value, and polygenic disorder} has bit by bit become a governable chronic disease. At this time, you may assume that within the battle against polygenic disease, humankind has firmly latched within the triumph, so solely a bit improvement in hypoglycemic agent is enough. To be honest, the scientists previously thought therefore too. the sunshine of hypoglycemic agent is just too dazzling. they need seen too several skinny and dying patients just like the very little boy Thomson, WHO quickly become alive and kicking when the hypoglycemic agent injection. within the history of humankind, there's very no drug which will win the sorcerous impact of hypoglycemic agent.
The magic of hypoglycemic agent makes doctors consciously or unconsciously unnoticed a very important detail. The detail is that some patients get immediate results when hypoglycemic agent injection, these patients area unit principally young children; whereas some patients when hypoglycemic agent injection, the impact isn't obvious, these patients area unit principally old individuals with fat bowels. In fact, as early as over 1500 years agone in ancient Bharat, doctors had already ascertained the distinction between the 2 kinds of "childhood" and "obese type" polygenic disease. Of course, doctors aren't invisible to those variations, however once the unhealthful mechanism isn't clear, hypoglycemic agent is clearly the most effective option to treat polygenic disease.

In January 1936, British physician Harold Simworth published a study on the classification of diabetes, which allowed people to understand that diabetes with the same symptoms had very different pathogenic mechanisms. The little boy Thomson was actually suffering from an autoimmune disease. The cause was that the immune system accidentally killed the insulin-producing pancreatic beta cells. The body of these patients cannot make insulin. What they face is an absolute shortage of insulin. Therefore, long-term insulin injections are very effective for such patients. We call this type of diabetes type I diabetes, and type I diabetes patients account for only 10% of the total number of diabetic patients Another type of diabetes is a metabolic disease. Obesity, unhealthy diet, lack of exercise and other reasons make the body lose its response to insulin. The pancreas of these patients did not have any disease, but the ability of insulin to regulate blood sugar decreased. In such patients, the effect is not obvious by simply injecting insulin. We call this type of patient type 2 diabetes. To deal with type II diabetes, which accounts for 90% of the total number of diabetic patients, we still need a specific hypoglycemic agent. The rise of metformin In 1949, Philippine doctor Garcia pointed out in a case he wrote: Metformin can effectively lower the patient's blood sugar without causing adverse reactions. Subsequently, French diabetics re-evaluated the hypoglycemic research on guanidine compounds in the past few decades on the basis of Garcia, and once again affirmed the value of metformin. However, metformin was still tepid, and it was not until 1957 that it was first approved for marketing in France. In 1997, British scientists published a large sample study of metformin that spanned 20 years. These evidence-based medicine data are powerful and convincing. This allowed the birth of metformin, which was born at the same time as insulin, to restore its due. The status of arena. End Since humans have acquired artifacts such as insulin and metformin, most people with diabetes can live as healthy as normal people as long as they take drugs as prescribed and adopt an active lifestyle. However, we have to admit that for humans, diabetes is still a disease that can be controlled but cannot be cured. There is also a very ambitious goal in front of scientists, which is to completely cure diabetes. Although we do not yet know when the day when diabetes is completely cured, we have reason to believe that with the advancement of science and technology, this day will not be far away. Source https://en.wikipedia.org/wiki/Metformin#History https://en.wikipedia.org/wiki/Stanley_Cohen?wprov=srpw1_0 https://en.wikipedia.org/wiki/Herbert_Boyer https://www.worldcat.org/title/principles-of-diabetes-mellitus/oclc/663097550 https://en.wikipedia.org/wiki/Harold_Percival_Himsworth https://www.idf.org/aboutdiabetes/type-1-diabetes.html https://www.idf.org/aboutdiabetes/type-2-diabetes.html https://en.wikipedia.org/wiki/Metformin#cite_note-Witters-131