Frederick Banting and Charles Best discovered insulin during the summer of 1921 at the University of Toronto. Since then, this seminal discovery has saved millions of diabetic patients. Before the discovery of insulin, from 1915 to 1922, physicians Frederick Madison Allen (Univ. of California) and Elliot Proctor Joslin (Harvard Medical School) promoted a strict diet with low carbohydrate intake as the main treatment for people diagnosed with diabetes.
Surgeon Frederick Banting and his assistant, the physiology and biochemistry student Charles Best, performed experiments to isolate insulin from the pancreata of dogs. They conducted these experiments in the laboratory of physiology professor John James Rickard Macleod.
During their experiments, Banting and Best treated dogs with canine pancreatic extract and observed that this treatment alleviated the symptoms of severe diabetes in dogs. In the winter of 1921, Dr. James Bertram Collip (Univ. of Alberta) aided the duo by purifying the pancreatic extract from cattle, permitting its safe testing in humans. In January 1922, a 14-year-old boy named Leonard Thompson became the first person with diabetes to be treated with insulin at Toronto General Hospital. Within 24h of insulin infusion, Thompson’s alarmingly high blood glucose levels regulated to near-normal levels. The Nobel Prize in Medicine was awarded to Banting and Macleod in 1923 for this incredible finding. They shared this award with Best and Collip, crediting this decision to their pivotal roles in the discovery of insulin.
Since 1921, insulin production has skyrocketed, and numerous variations and formulations of insulin have been developed. Eli Lilly was the first company to produce insulin on a large scale in 1923, making insulin widely available in North America. Three years later, Johns Hopkins University professor John Jacob Abel discovered a technique to crystallize insulin in small amounts in attempts to purify the insulin molecule. In the University of Toronto’s Connaught Laboratories, David Aylmen Scott worked to improve this insulin crystallization process. In 1933, with support from Arthur F. Charles and Albert M. Fisher, Scott enhanced the crystallization of insulin by adding small quantities of zinc to a buffered insulin solution so that great amounts of insulin could be purified.
To decrease the number of necessary insulin administrations, in 1946, Hans Christian Hagedorn formulated NPH (Neutral Protamine Hagedorn) insulin, whose pharmacokinetics permits slower expulsion from the body.
Additional improvements to insulin formulation continued in 1978 by David Goeddel and his coworkers at Genentech, who developed a recombinant DNA human insulin using the bacteria E.coli. This permitted the use of human insulin in place of insulin extracts from cattle and pig, which induced an allergic reaction in many patients.
This development involved insertion of the human insulin gene into bacterial DNA. Recombinant expression of human insulin by E. coli in bioreactors were collected and purified. The technique to crystallize insulin discovered by Scott was also utilized in the collection and purification of human insulin. In 1982, human insulin became available to treat patients with diabetes, substantially increasing the amount of insulin produced.
To better control blood glucose levels, different variations of insulin that mimic the patterns of insulin secretion in the body such as basal and prandial insulin secretion were identified. Basal insulin refers to baseline levels of insulin when not eating and drinking, whereas prandial insulin is secreted after eating in response to rises in blood glucose. In 1996, insulin analogues were developed. These synthetically derived insulin analogues are generated by modifying the amino acids of the insulin molecule to alter its pharmacokinetics. Lispro, the first prandial insulin analogue, became available in 1996, and a basal insulin analogue glargine was accessible in 2000.
Furthermore, there have been significant technological advances in how a diabetic person manages their condition. In the 1970s, portable glucose meters became commercially available, permitting self-monitoring of blood glucose levels. In 1983, insulin pumps, which are small wearable devices that release insulin subcutaneously through a needle, became widely accessible. The pump can be programmed to deliver insulin during the day. Compared to self-administering multiple injections per day with numerous needles, this is a method of insulin administration that is both more simplistic and precise.
In 1985, insulin pens loaded with insulin became available as another way to administer insulin. Insulin pens permitted more simplistic and precise self-administration of insulin relative to the use of a syringe and vial of insulin.
To further improve self-monitoring of blood glucose levels, the first continuous glucose monitoring (CGM) device was approved by the FDA in 1999. Modern CGMs may be paired with an insulin pump to adjust the amount of insulin released throughout the day.
Individuals with diabetes currently have the option to choose various formulations of insulin and methods to self-monitor their condition, which ultimately grants increased autonomy over their health. Many more people with diabetes will benefit from future developments in insulin and technologies for delivering insulin and monitoring blood glucose, as well as the potential discovery of a cure for diabetes.
Faizah Numa Sayeed
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