Innovators & Pioneers
Charles Herbert Best was most renowned as co-discoverer of insulin with Frederick G. Banting. Insulin, which is a hormone secreted by the pancreas, regulates the level of sugar in the blood. Its discovery in 1921 led to its use as a treatment for diabetes, which until that time had led swiftly to emaciation, coma, and death. Later in his career, Best assisted in the establishment of associations of diabetics to promote support groups and educational programs for their members. He also did important research on the nutrient choline and the blood anticoagulant heparin.
Best was born on February 27, 1899, in West Pembroke, Maine, a town near the border of the Canadian province of New Brunswick. His parents were Canadian citizens, both originally from Nova Scotia. Best was a direct descendant of Major William Best, who in 1749 was one of the founders of Halifax, Nova Scotia. Best's father, Herbert Huestes Best, was a country doctor whose practice straddled the U.S.-Canadian border. As a teenager, Best often accompanied his father on his rounds in a horse-drawn buggy. Best's mother was Luella Fisher Best.
After finishing high school, Best entered the University of Toronto in a liberal arts program. When World War I interrupted his education, he served as a sergeant in a regiment of the Canadian Tank Corps. He returned to Toronto in 1919 after the war to complete his education, but switched his course of study to physiology and biochemistry in preparation for a medical degree. Best played professional baseball in order to finance his education. He received his B.A. in 1921. In May of 1921, Best's physiology professor, John James Rickard Macleod, introduced him to Frederick Grant Banting, a 29-year-old orthopedic surgeon from London, Ontario. Best had worked as a research assistant for Macleod and planned to begin studying for [a] master's degree under him in the fall. Banting would be using Macleod's lab during the intervening summer to do experiments to find out the function of the pancreas in preventing diabetes, and he needed an assistant to help with analyses of blood chemistry. Another of Macleod's students was also interested in the job, so he and Best flipped a coin. Best won. On May 17, 1921, the day after he completed his examinations for his undergraduate degree, Best began working with Banting. It was a collaboration that would set the course of his career.
Discovers Treatment for Diabetes
Experiments done 30 years earlier had shown that when a dog's pancreas was removed by surgery the animal developed the symptoms of diabetes: it would grow insatiably thirsty, begin excreting large amounts of sugar in its urine, and then become listless, go into a coma, and die. Banting's idea was that the pancreas must secrete something in addition to its digestive enzymes in order to prevent this process. He was convinced that the crucial substance would be found in groups of cells on the pancreas called the islets of Langerhans. These cells could be isolated by tying off a dog's pancreatic ducts; the rest of the pancreas would atrophy after several weeks, but the islets of Langerhans would remain intact. An extract could then be made from the cells and injected into a diabetic dog. If Banting's idea was right, such an extract would relieve the symptoms of diabetes.
The way he originally planned the work, Banting would do the surgery, removing the pancreas from some dogs to make them diabetic and tying off the pancreatic ducts in others to isolate the islet cells. Best would do blood and urine tests on the dogs. As the research progressed, however, Best learned to do some surgery too. Best, for his part, had a personal interest in diabetes. His father's sister, who had lived with the Best family in West Pembroke, had died in a diabetic coma in 1918.
Banting and Best had expected to spend only eight weeks on their study. But it was July 30 before they were ready to prepare the extract. On that day, Banting removed the shriveled pancreas from a dog whose ducts had been tied. He and Best prepared an extract from it by chopping the pancreas into small pieces, grinding it in a chilled mortar with salt water, and filtering the mixture through cheesecloth. A blood sample from the diabetic dog showed its blood sugar level to be 0.2. Banting and Best injected some of their extract into the dog. An hour later its blood sugar level had dropped to 0.12. After another injection it registered 0.11. This dog died the next day, presumably from an infection. But Banting and Best were encouraged by the result and tested their extract on more diabetic dogs. They called the extract "isletin."
During the following months Banting and Best performed additional experiments to confirm and explain their results. With an injection of their extract they could revive a diabetic dog from its coma and prevent its imminent death. They found ways of obtaining the extract more easily and in larger quantities from the pancreases of fetal calves obtained from a local slaughterhouse. Macleod, who had been vacationing at his home in Scotland during the summer, returned in September and made suggestions for further studies. He also hired James Bertram Collip, a Ph.D. biochemist, to help purify the active component of the extract. Best continued with the work, but also began his M.A. program at the University of Toronto. That fall Banting and Best wrote their first paper describing the experiments with dogs, titled "The Internal Secretion of the Pancreas." It was accepted for publication in the February 1922 issue of the JOURNAL OF LABORATORY AND CLINICAL MEDICINE.
By the time the paper was published, however, Banting and Best had already treated a human diabetes patient with the extract. They had also begun to call their extract by the now familiar name of insulin, at the suggestion of Macleod. The word "insulin" is based on the Latin word for island. The first patient to receive insulin was 14-year-old Leonard Thompson, who was so weak after two years of suffering from diabetes that he had been admitted to Toronto General Hospital. Thompson's weight was down to 65 pounds, and his doctors expected him to live for only a few more weeks. Before administering insulin to the boy, Banting and Best performed a perfunctory clinical trial: they injected each other with their extract. Since there seemed to be no side effects other than soreness around the injection, in January 1922 they went ahead and treated the boy. After an initial problem with impurities in the insulin was solved, his condition began to improve. He regained his energy and put on weight. Thompson lived another 11 years, dying in 1935 from pneumonia contracted after a motorcycle accident. This success, a literal pulling back of a diabetic child from the brink of the grave, was repeated again and again in the next months, as insulin became a standard treatment for diabetes.
Nobel Committee Leaves Best Out
The 1923 Nobel Prize in physiology and medicine for that year was awarded to Banting and Macleod for the discovery of insulin. Banting was furious. In his opinion, Macleod had done little more than provide laboratory space, whereas Best had shared the work of research. Best was in Boston the day the news arrived, giving an address to medical students at Harvard. Banting immediately sent Best a telegram stating that he would share both the credit for the discovery and the Nobel Prize cash award with Best. Macleod, who considered the work a collaboration, divided his portion of the prize with Collip.
Best continued his studies, receiving his M.A. in 1922 and his M.D. in 1925, while also working on a commercial process for producing insulin. At the same time he received the M.D., Best was also awarded the Ellen Mickle Fellowhip for highest standing in the medical course. During the years Best was doing insulin research he had been courting Margaret Mahon, writing her love letters that also included details about the experiments on dogs. She was so well versed in the work that she helped Banting and Best write their first paper about it. Best married Margaret Mahon in 1924, and later they had two sons. In 1926 the couple sailed to England, where Best spent two years doing postgraduate research in the laboratory of Sir Henry Dale in London. This research led Best to the discovery of histaminase, an anti-allergic enzyme. He received his doctorate from the University of London in 1928.
Before the degree was awarded, however, Best had returned to the University of Toronto in 1927 to head the department of physiological hygiene, a post he held until 1941. In 1929, when Macleod retired, Best was also made chair of the department of physiology. He was just 30 years old at the time. He remained in that position until 1965.
Best's study of insulin led him to a related avenue of research. He had noticed that the laboratory dogs whose pancreases had been removed to render them diabetic developed fatty livers, similar to cirrhosis of the liver in alcoholics. Best and his colleagues found that feeding such dogs lecithin prevented this change in the liver. In the 1930s they isolated choline as the active nutritional component of lecithin, a component found in the cells of many plants and animals, and did studies on the role of choline in metabolism. In the 1930s Best also became interested in heparin, which had just been discovered. He recognized that heparin could be an important anticoagulant drug for preventing blood clotting and went to work purifying it for human use. With the outbreak of World War II, Best continued his research interest in blood. He established the Canadian project for supplying dried blood serum to the wounded overseas and personally worked collecting blood from volunteers. This project was a predecessor to the blood transfusion service of the Red Cross. In 1941 Best was appointed director of the medical research unit of the Canadian Navy. In this capacity he coordinated studies to find ways to enhance night vision and to remedy motion sickness.
A Friend to Diabetics
In 1941, Frederick Banting was killed in a airplane crash en route to a wartime mission. After Banting's death, Best took over his directorship of the Banting and Best department of medical research at the University of Toronto. Best also worked to organize associations of diabetics that provided support groups and educational programs for their members, including summer camps for diabetic children. He was president of the American Diabetes Association from 1948 to 1949 and remained honorary president thereafter. He was also honorary president of the International Diabetes Foundation. In 1953 the University of Toronto named a new building for medical research the Best Institute. The same year, Best became the first president of the International Union of Physiological Sciences.
Best retired from the University of Toronto in 1965. In 1966 friends of Best purchased Best's parents' clapboard house in West Pembroke, Maine and gave it to the American Diabetes Association. Later the home was proposed to the U.S. National Trust for Historic Preservation as a cultural landmark and turned into a museum. Best spent his retirement years traveling around the world with his wife, who was a historian and a botanist, visiting friends and colleagues.
Best received scores of medals, awards, and honorary degrees and was praised by the Pope, the Queen of England, and other heads of state. He wrote numerous scientific articles, and was co-author of a widely used physiology textbook. In March of 1978 one of Best's sons died of a heart attack. Hours after hearing the news, Best himself collapsed from a ruptured blood vessel in his abdomen. He died several days later, on March 31, 1978, at Toronto General Hospital.
Source: From NOTABLE TWENTIETH-CENTURY SCIENTISTS. Gale Research, 1995. Reprinted by permission of The Gale Group.
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