Smallpox, Syphilis and Salvation

by Sheryl Persson

  ‘In my father’s view, as in Fred Banting’s,’ Henry Best said, ‘the Nobel Prize should have gone to Banting and Best, rather than to Banting and Macleod.’[33] He said that his father rarely talked about this but he had no doubt that the issue played on his father’s mind later in his life. It is probably a matter of opinion as to whether Charles Best was simply overlooked or deliberately sidelined.

  There have been many people who felt that they or others should have received credit for the discovery of insulin, aside from those in Toronto. There was Ernest Scott in the United States, whom the Toronto team had acknowledged; and Nicolas Paulesco in Romania, whom they had not. However, surely this goes to the nature of what constitutes a discovery? As medical research has become more sophisticated and complex, scientists increasingly base new research on earlier discoveries and more and more people have a hand in each new development. It was perhaps different centuries ago when Edward Jenner discovered a vaccine for smallpox, but even then Jenner had been aware of folklore and earlier procedures such as variolation, all of which informed his research.

  At the 1991 Meeting of the International Diabetes Federation in Washington DC, Henry Best spoke with Professor Rolf Luft of Stockholm’s Karolinska Institute, the body that awards the Nobel Prizes. Following the meeting Professor Luft wrote to Best to say that after the passing of so many years and so much debate, with reservations, he thought that it might have been fair to have awarded the Nobel Prize to Banting, Best and Paulesco.[34] The method of selecting Nobel laureates is complex and the choices do not always meet the approval of individuals or their supporters. When one person is pushed forward the role of others might be negated. Banting and Macleod were each nominated separately by American proposers and then jointly by Professor August Krogh, a Danish Nobel laureate.

  During his speech to the Academy of Medicine in 1996 Henry Best read out a Resolution passed by the Council of the Academy on 23 March 1923 in regard to the discovery of insulin. It stated that:

  ...in view of the importance of the discovery and isolation of a substance purporting to be the internal secretion of the pancreas controlling carbohydrate metabolism, and consequently of great value in the science of Physiology and Biochemistry, and possibly, in practical medicine by reason of its presumed ability to control Diabetes Mellitus, the Council of the Academy of Medicine, after careful investigation, believes that conclusive evidence has been furnished of: FIRST the isolation of such a substance from the pancreas of various animals and termed ‘insulin’ by Dr. F.G. Banting and Dr. C.H. Best in the summer of 1921 at the University of Toronto.[35]Although the significance of the discovery is qualified there is no uncertainty about who the discoverers were. However, Charles Best was referred to as Dr Best, a title he did not actually have until 1925. Henry Best felt that the council’s statement was possibly a reflection of the subliminal belief that someone who was not yet a medical doctor or did not have a PhD could not really have been a co-discoverer of insulin and therefore could hardly be a contender for the Nobel Prize. As with all medical breakthroughs, when fame and money are at stake emotions can be extraordinarily volatile.

  From various accounts it would seem that Charles Best had a reasonable relationship with John Macleod, always referring to him with deference as his professor. Macleod had taught him the physiology he used in his insulin work. Best, according to his son, believed that Macleod was influenced by his European experience of the way discoveries were recognised and that the possibility of fame may have affected his judgment. It was not that Macleod had promoted his own claim unfairly, but that he had neglected to present the case for Best. The relationship between these two men was not severed, and although later in life Best was concerned about how things had turned out, he saw Professor Macleod during trips overseas after the older man returned home in 1928 to Aberdeen in Scotland.

  As for Best and Collip, they had a cordial working relationship but were never close friends and there were always underlying tensions. Charles Best was uncomfortable talking in public about the discovery of insulin when Collip was present and carried with him the memory of an incident in January 1922 when an argument between Banting and Collip about the purification of insulin had apparently become physical. Charles Best wrote to his father on 10 May 1922 that there had been ‘a lot of trouble, quarrels etc., but we are getting on’. Collip left the laboratory at that time and Best told his father in the letter, ‘I am now in charge of making the dope.’[36] He was only 22 years old.

  James Collip went on to become a distinguished researcher and administrator at a number of Canadian universities as well as the National Research Council and was a leading endocrinologist and worldwide authority on the properties of insulin. He accepted the Chair of Biochemistry at McGill University, where he conducted extensive studies on hormones. In 1941, he became Chairman of McGill’s new Institute of Endocrinology and capped off a brilliant career as Dean of Medicine at the University of Western Ontario.[37]

  In recalling the events of 1921 and 1922, at the request of Sir Henry Dale, a distinguished scientist, Nobel laureate and President of the Royal Society who became Charles Best’s greatest mentor, Best wrote on 22 February 1954:

  I have to confess that even after all these years, the revival of the memory that Professor Macleod and later Collip, instead of being grateful for the privilege of helping to develop a great advance, used their superior experience and skill, with considerable success, in the attempt to appropriate some of the credit for a discovery which was not truly theirs, still makes me warm with resentment. I must state, also that I have only to think of the understanding and fairness of scientific colleagues in many countries who have read our reports carefully, to replace resentment with a much better feeling.[38]Charles Best was not the first or the last scientist to feel such resentment.

  Frederick Banting’s reaction to the announcement that Macleod, not Best, was to share the Nobel Prize is probably best shown by the telegram he sent to a colleague in Boston where Best was about to make a speech. The telegram said:

  At any meeting or dinner, please read the following stop I ascribe to Best equal share in the Discovery stop hurt that he is not so acknowledged by Nobel trustees stop will share with him stop.[39] As for Professor Macleod, there are those who feel he was treated unfairly in the insulin wash-up. It was a period of frantic activity before and after the discovery. Macleod worked to promote the distribution of insulin around the world and co-authored a series of papers on its use and actions. The pro-Macleod camp feels that the bitter infighting that followed the great discovery was the result of Banting forcefully promoting his own role in the discovery. Banting is accused of lacking the scientific background to appreciate the value of the advice and contributions that Macleod and Collip made to the work. Macleod has been described as a reserved and modest man who was not equipped to stand up to the campaign waged against him—but that may be selling Macleod short in one way.[40] He was actively involved in the research program and, according to some, provided the conclusive demonstration that insulin comes from the pancreatic islets.

  John Macleod left Toronto in 1928 (it is said with some relief) to become Regius Professor of Physiology at Aberdeen University, a post he held until his death. His published output was phenomenal, although his final years were marred by ill health from progressive rheumatoid arthritis. He died at his home on 16 March 1935, aged just 58. His supporters say the accusations that he stole the credit for work done by his juniors did lasting harm to his reputation and his contributions to the discovery of insulin were largely forgotten following his death.

  In more recent times the debate was in evidence again when a disagreement arose about changed wording on a plaque outside the medical sciences building at the University of Toronto. It commemorates the work done in the old medical building in 1921. On the original plaque Banting and Best were acknowledged as the co-discoverers of insulin. At the beginning of the 1990s this was changed to Banting, Best, Collip and Macleod. />
  When asked about his reaction to a Canadian TV program about the discovery of insulin—the theme of which is obvious from its name, Glory Enough for All—Charles Best’s son said that some of the characters and events had been fictionalised but, as is the case with extraordinary breakthroughs in science and medicine, the real story is dramatic enough without invention.[41] It is no wonder that humans, being the flawed creatures that we are, with our vanities and foibles, are reluctant to share fame and fortune and so often there is not ‘glory enough for all’.

  ***

  After the discovery of insulin in 1921 Frederick Banting became a popular hero and a force in medicine in Canada. When his work on insulin was complete he undertook research into heart disease and cancer. Banting’s broken relationship early in his career had left him free to devote himself to research. His fame after the award of the Nobel Prize in 1923, combined with his charming personality and sense of humour, made him a sought-after marriage prospect and in 1924 Frederick Banting married Marion Robertson. They had one child but the marriage ended unhappily in divorce.

  Both Banting and Best received offers to leave Canada to carry out research in the United States, but neither did. There was a continuous shower of glory, awards and honorary degrees for Banting, and an institute bearing his name, the Banting Institute, was opened in 1930. In 1934 Frederick Banting was knighted, some years before Charles Best. Frederick Banting married again in 1939. His second wife was Henrietta Ball but the marriage was destined to be a short one, this time for a different reason. Sir Frederick Banting met with a tragic early death. He had joined the army and was serving as a major with the Medical Corps when in February 1941, on one of many flights that he made from Canada to England, the plane crashed into a lake at Gander in Newfoundland. Frederick Banting had not reached his 50th birthday. His memory is perpetuated, however, as the lake is now known as Banting Lake.

  Henry Best surmised that Charles Best probably received more honours than would have come his way if Banting had lived. Best’s was a long and illustrious career. When visiting Toronto in 1922, Sir Henry Dale asked Best to come to the National Institute for Medical Research in London but he stayed in Canada and continued working with Banting at the Banting and Best Department of Medical Research at the university and completed doctorates in both medicine and physiology. Best did spend time abroad between 1925 and 1928 while doing postdoctoral work at the University of Freiburg in Germany and the University of London in England.

  By 1929 Charles Best had been appointed head of the University of Toronto’s physiology department. He returned to Canada to take up the position and resumed his work as research associate in the Banting and Best Department of Medical Research. As time progressed, Frederick Banting and Charles Best developed different research interests. Best’s work had a high public profile. He successfully isolated and purified heparin, an effective anti-coagulant for the treatment of thrombosis, investigated histamine and conducted research into the vitamin choline.[42]

  According to his son, Charles Best’s ambition possibly irritated Banting. Those who knew Best describe him as ambitious, not just professionally but for his family, his colleagues and his students. However, in 1933 Best turned down an offer to succeed Sir Edward Sharpey-Schäfer to the Chair of Physiology in Edinburgh. Best’s ambition did not override his loyalty to the University of Toronto.

  During World War II Charles Best joined the Royal Canadian Navy and directed the Medical Research Unit. Working with the Red Cross and the Canadian government he was involved in wartime projects developing night lighting, remedies for seasickness, and the design and equipping of survival rafts. He also collaborated on devising a method for transforming human blood into dried blood serum (plasma) that could be stored indefinitely.[43] Research took on a different focus in wartime but it was still about survival. In 1941 Best found himself taking over the role of director of the Banting and Best Department of Medical Research but it was not a cause for celebration, coming as a result of Banting’s unexpected and tragic death.

  In 1949 the post of secretary of the Medical Research Council of Great Britain was offered to Best followed by another offer in 1951, the Chair of Physiology at Cambridge. But Charles Best could not be tempted to leave the University of Toronto. He had been promised his own building, where he could combine the two departments he headed, Physiology and the Banting and Best Department of Medical Research. That building, the Charles Best Institute, was finally opened in 1953 and became a centre of further outstanding research.

  Honours and awards came later to Best than to the older scientists involved in the discovery of insulin. The four main contenders became Fellows of the Royal Society of London: Professor Macleod in 1923, James Collip in 1933, Frederick Banting in 1935 and Charles Best in 1938. James Collip received the CBE (Commander of the British Empire) in 1943 and Best received the same award in 1944. The first of Best’s 30 honorary degrees was presented at the 50th Anniversary Convocation of the University of Chicago on 29 September 1941. Charles Best was also awarded the Companion of the Order of Canada in 1967 and the Companion of Honour in 1971.

  Charles Best had a sense of humour. He was awarded Membership in the Papal Academy of Sciences. The parchment accompanying the gold medallion stated that henceforth Charles Herbert Best should be addressed as ‘Your Excellency’ and he often quipped at home that he should be addressed by his full title. When giving lectures and talks to audiences which included a number of Roman Catholics he would say that the Holy Father, the Pope, was getting good advice on matters such as birth control from the nephew of an Anglican Bishop and the son-in-law of a Presbyterian Minister.[44]

  Best enjoyed the life that success and fame brought him but he also enjoyed simpler pleasures and retained an affinity with the small village of West Pembroke where he grew up. Horses had been a part of his childhood and he never lost his love of riding and kept his father’s horses on a farm that he bought close to West Pembroke. Interestingly, both Charles Best and Frederick Banting had a deep interest in painting (shades of Louis Pasteur) which Best found totally absorbing and relaxing, a foil to the pressures of his medical life.

  The inexhaustible energy and enthusiasm for life that Best had always exhibited began to wane in 1953 when he suffered a series of heart attacks. He made a good recovery but a decade later in 1964 he experienced the onset of a sudden and severe depression from which he never quite recovered. Charles Best did, however, enthusiastically take part in the celebrations surrounding the 50th anniversary of the discovery of insulin in 1971. During that and the following year he and Margaret travelled extensively, having been invited to events in Brazil, England, Israel and many countries in Europe. On 3 September 1974, the devoted couple celebrated their 50th wedding anniversary.[45] Margaret had always exercised a degree of influence in the relationship. She travelled everywhere with Charles, except during World War II when his trips overseas caused her great anxiety. Margaret was afraid her husband might meet the same fate as Frederick Banting.

  On Easter Sunday, 1978, Charles Best suffered an aneurysm of the aorta the day after one of his sons, Sandy, died of a massive heart attack at the age of only 46. Five days later Charles Best, aged 79, was also dead. For Margaret Best, it was a terrible double blow.

  Posthumously Charles Best was inducted into the Canadian Medical Hall of Fame in 1994 and in 2004 he was inducted into the National Inventors Hall of Fame. He has been honoured on stamps in his own country and in Belgium, Croatia and Uruguay. In 1971 Kuwait issued a set of two stamps showing portraits of Frederick Banting and Charles Best and featuring a syringe. This is a reminder of just how far-reaching and significant the work of the co-discoverers of insulin has been to humankind. Although not a cure for diabetes, insulin has saved the lives of millions and today most sufferers lead relatively normal lives. Each day diabetics all over the world hold in their hands the physical evidence of the gift given to them by two exceptional scientists. Theirs is a daily dose of salvation. />
  DEVELOPMENTS IN INSULIN AND DIABETES RESEARCH

  The production of insulin has changed a great deal since 1922 when Frederick Banting and Charles Best first successfully extracted it from a dog’s pancreas. In May 1922 Eli Lilly and Company and the University of Toronto entered into an agreement for the mass production of insulin in North America.[46] In the first successful commercial insulin preparations from cows and later pigs—the chemical structure of insulin in these animals is only slightly different to human insulin—the pancreatic islets and the insulin protein contained within them were extracted from animals slaughtered for food in a similar but more complex process than was used by Banting and Best.[47] Bovine and porcine insulin still work well for many people although some people are allergic to foreign or non-human protein.

  In 1936 researchers found a way to make insulin with a slower release in the blood. They added a protein found in fish sperm, protamine, which the body breaks down slowly.[48] One injection lasted 36 hours. Professor Macleod was involved in research associated with this development. Another breakthrough came in 1950 when a type of insulin was produced that acted slightly faster and did not remain in the bloodstream as long. In the 1970s research began on producing insulin that better mimicked how the body’s natural insulin worked, releasing a small amount all day with surges occurring at mealtimes.