Best, Charles Herbert
BEST, CHARLES HERBERT
(b. West Pembroke, Maine, 27 February 1899; d. Toronto, Canada, 31 March 1978)
Best was the son of Herbert Huestis Best, a Canadian-born general practitioner, and of Luella May Fisher Best. The highlight of Best’s medical research was his involvement in the discovery of insulin in the years 1921 and 1922. What began as a summer research job for a bright student turned into one of the most exciting and controversial medical adventures of modern times. After the discovery, Best finished his education and embarked on a long, productive career as a physiologist at the University of Toronto. He received much acclaim and many honors for the insulin work and considered himself one of the codiscoverers of insulin. On 3 September 1924 he married Margaret Hooper Mahon; they had two sons.
Best completed his bachelor’s program in physiology and biochemistry at the University of Toronto in May 1921 and was hired for the summer as a research assistant to John J. R, Macleod, a professor of physiology. In May, Macleod asked Best and the other student assistant, Edward Clark Noble, to help test Frederick G. Banting’s hypothesis that ligation of the pancreatic ducts in living animals (dogs) would cause selective degeneration of pancreatic cells and permit the isolation of the much-sought antidiabetic internal secretion. Best won a coin toss to see who would work first with Banting; Noble later decided it would be convenient for Best to finish the assignment.
Best did all the chemical tests for Banting, measuring blood, urinary sugars, and urinary nitrogen in the series of experiments on depancreatized, ductligated, and normal dogs. Late in July. Banting and Best began injecting extracts of degenerated pancreas into depancreatized diabetic dogs and recorded frequent declines in blood sugar after the injections. These experiments were repeated and extended at intervals through October and November and were reported in Banting and Best’s first paper, “The Internal Secretion of the Pancreas,” presented on 30 December 1921 at the American Physiological Society meeting at Yale and published in the Journal of Laboratory and Clinical Medicine in February 1922.
Historical re-creation of Banting and Bests experiments, based on their complete notebooks, indicates that their achievement was similar to that of other researchers, including E. L. Scott Israel S. Kleiner, and Nicolas C. Paulesco, all of whom had been able to produce pancreatic extracts that often reduced hyperglycemia or glycosuria. Lacking both training and expertise, though possessing boundless enthusiasm, Banting and Best understood neither the advances made by co-workers nor the limitations of their own papers. Their papers were marred by factual errors and misinterpretations, a serious misrepresentation of Paulesco’s work (based on Best’s translation error), and failure to assess Banting’s original, erroneous assumption that the external and internal secretions are antagonistic within the pancreas.
Macleod, whose instructions for preparing saline extract of chilled pancreas were vital to Banting and Best’s early successes, was impressed by their pattern of favorable results and by Banting’s stubborn optimism. New research was begun, under Macleod’s direction, involving Banting, Best (now a master’s student), and an experienced biochemist. James B. Collip. In December 1921 the team made rapid advances in extractive technique—utilizing fresh pancreas in acid alcohol—and in the exploration of the extracts’ antidiabetic properties.
Banting’s temperament clashed with Macleod’s in virtually every way. He began to feel that he and Best were being shunted aside in the work and insisted that they should be responsible for preparing the first extract to be used in clinical tests. Macleod consented. Assisted by Banting, Best made extract tested on a patient, fourteen-year-old Leonard Thompson, in Toronto General Hospital on 11 January 1922. The extract was not effective enough to justify further administration. Tests on Thompson resumed on 23 January, using purified extract made by Collip. The spectacular antidiabetic effects of Collip’s extract demonstrated to the Toronto group that they had made a very big discovery. In May 1922 they announced their discovery of insulin and its therapeutic benefits for diabetics, in “Effect Produced on Diabetes by Extracts of Pancreas,” in Transactions of the Association of American Physicians.
Best studied the extract’s effect on the respiratory quotient of human diabetics for his master’s thesis. As part of the collaborating group, he was a joint author of all their major papers, his name following Banting’s in the agreed-upon alphabetical order. In the spring of 1922, he returned to the extraction problem because technical difficulties had caused Collip to lose the ability to make insulin. Best was instrumental in the group’s rediscovery of an extractive technique, and when Collip left Toronto in June 1922, to return to the University of Alberta, Best replaced him as director of insulin production at Toronto University’s fledgling Connaught Laboratories. From this time, however, production advances were made principally by Eli Lilly and Company, with whom the Canadians had decided to collaborate.
When Banting learned that he and Macleod had been awarded the 1923 Nobel Prize in physiology or medicine for the discovery of insulin, he immediately announced that he was sharing his half of the prize money equally with Best. His generous allocation of credit to Best stemmed largely from the moral support his assistant had given him at several points during both the research and the vicious quarreling with Macleod and Collip, Best was disappointed not to have received more formal recognition for his insulin work.
Best completed his medical training in Toronto in 1925 and did postgraduate research under Henry H. Dale at the National Institute for Medical Research and the University of London, receiving the D.Sc. in 1928. He was given an appointment in the School of Hygiene at the University of Toronto, and in 1929 he succeeded Macleod as professor of physiology. In 1941 he succeeded Banting as head of the Banting and Best Department of Medical Research. Best’s later research centered on explorations of the lipotropic effects of choline and on various insulin-related problems. In the late 1930’s Best’s laboratory pioneered in the isolation and production of heparin, which soon found an important clinical application as an anticoagulant in vascular surgery. Other research ranged from early studies in exercise physiology (using 1928 Olympic marathon runners) to wartime work on night vision and seasickness. With Norman B. Taylor, Best coauthored a widely used textbook. The Physiological Basis of Medical Practice (Baltimore, 1st ed., 1937, 10th ed., 1979), He wrote and reminisced often about his role in the discovery of insulin, but his memory was too selective to make his accounts entirely reliable.
I. Original Works. The Fisher Rare Books Library at the University of Toronto and the university archives contain several major collections of documents relating to the discovery of insulin. The Banting papers include the Banting and Best notebooks. The Macleod papers and the records of the university’s Insulin Committee are also important. Most of the documents in the extensive Best collection are from a later period, but many important autobiographical transcripts are contained in the papers of Best’s chosen biographer, W. R. Feasby. The Best-Dale correspondence in the H. H. Dale papers at the Royal Society of London is also illuminating. Documents relating to the discovery of insulin that Dale and Best deposited in the Wellcome Institute are duplicated at Toronto.
Best’s most important account of his role in the discovery, written in September 1922, was published as part of “Banting’s. Best’s, and Collip’s Accounts of the Discovery of Insulin,” in Bulletin of the History of Medicine. 56 (1982), 554–568. All of his important scientific papers. plus many reminiscences and fragments of autobiography, are in Selected Papers of Charles H. Best (Toronto, 1963). For the most complete bibliography of his publications and a list of his honors, see his obituary, by Sir Frank Young and C. N. Hales, in Biographical Memoirs of Fellows of the Royal Society, 28 (1982), 1–25.
II. Secondary Literature. The standard account of the discovery of insulin, the first to utilize the documents cited above, is Michael Bliss, The Discovery of Insulin (Chicago, 1982). Further detail is in Bliss. Banting: A Biography (Toronto, 1984), Earlier critical appraisals of Banting and Best’s researches are FfrangconRoberts, “Insulin” in British Medical Journal, no. 4833 (16 December 1922), 1193–1194, and Joseph H. Pratt, “A Reappraisal of Researches Leading to the Discovery of Insulin,” in Journal of the History of Medicine. 9 (1954), 281–289. The Royal Society obituary is somewhat incomplete and inaccurate, relying too heavily on Best’s later memories. Several versions of W. R. Feasby’s unpublished biography of Best are in the Feasby papers at the University of Toronto.
Charles Herbert Best
Charles Herbert Best
The Canadian medical scientist Charles Herbert Best (1899-1978) codiscovered insulin in 1921. He also discovered the enzyme histaminase, and his studies on choline established its importance as a dietary factor.
Charles H. Best was born on February 27, 1899, at West Pembroke, Maine. His parents, Dr. Herbert Huestes Best and Luella Fisher Best, were Canadian. Charles entered the University of Toronto in 1916, but interrupted his studies to join the Canadian army. After World War I he resumed his studies at the University of Toronto and graduated in May 1921.
Discovery of Insulin
The day after his examinations Best began work with Frederick Banting in the department of physiology. Best had been asked to assist in the chemical procedures involved in the research. He and Banting started their work on the extraction of pancreatic tissue and the treatment of depancreatized dogs. This project led to the discovery of insulin later that summer.
Best was appointed director of the Insulin Division of the Connaught Laboratories in January 1922. In 1924 he married Margaret Hooper Mahon, and in the following year, after he had received his medical degree from the University of Toronto, the couple went to England. There Best worked with Sir Henry Dale and obtained his doctorate from the University of London in 1928.
During his postgraduate work and throughout his medical training, Best continued to be actively involved in insulin production and studies on diabetes. He had numerous appointments at the University of Toronto; after Banting's death in 1941, Best became head of the Banting and Best Department of Medical Research.
Following the work on insulin Best continued his investigations in several different areas. In London he became interested in histamine. On his return to Toronto he and E.W. McHenry demonstrated the action of histaminase, an enzyme responsible for the breakdown of histamine. In 1928 Best organized a team to explore the sources of heparin and to test its effectiveness in the prevention of thrombosis.
Researchers had noted that after removal of the pancreas, and despite the use of insulin, the livers of dogs became swollen with fat. Best, with his colleagues J. M. Hershey, M. Elinor Huntsman, and others, investigated the cause of these fatty livers and found choline to be one factor preventing the development of fatty livers (a lipotropic factor). This was an important discovery since, when fatty livers do develop as a result of a deficiency of choline or related factors, fibrotic changes and, finally, cirrhosis may follow.
Best received honorary doctorates from 18 universities, and was the recipient of numerous medals, awards, and honors. He was a fellow of the Royal Society of London, the Royal Society of Canada, and the Royal College of Physicians and Surgeons of Canada.
Best retired from the University of Toronto in 1965 and spent much of his time traveling around the world with his wife. He died on March 31, 1978, in Toronto.
Information on Best and his work is in Arturo Castiglioni, A History of Medicine (trans. 1941; 2d rev. ed. 1947), G.A. Wrenshall, G. Heteny, and W.R. Feasby, Story of Insulin: Forty Years of Success against Diabetes (1962), and in Michael Bliss, Discovery of Insulin (1982). □