As we approach the week during which the 2023 Nobel Prizes will be announced (October 2-9, 2023), it is perhaps timely to consider the events that surrounded the first Nobel Prize awarded to a Canadian. Exactly 100 years ago, Frederik G. Banting and John R.R. Macleod, were awarded the 1923 Nobel Prize in Physiology or Medicine “for the discovery of insulin” at the University of Toronto.
Banting, was born in Alliston, a small town in Ontario and trained as a surgeon at the University of Toronto before serving on the front during World War I. Upon his return to Canada, he was unsuccessful in establishing his own medical practise and having (avowedly), ‘been inspired by a dream’, Banting approached John Macleod, a Professor at the University of Toronto, with his idea to isolate insulin in order to cure diabetes. Where this idea came from is somewhat unclear, as Banting did not, at that time, know anyone with diabetes nor was there anyone with diabetes in his clinical practice. However, as Banting was completely naïve to the process of scientific inquiry, Macleod was the ideal person to support Banting in this pursuit, as he had devoted most of his career to the study of carbohydrate (aka sugar) metabolism in the body. With the toss of a coin, Macleod selected Charles Best, an undergraduate science student, to assist Banting in the laboratory.
During the long, hot summer of 1921, Banting and Best toiled away in the laboratory with some, albeit limited success in isolating insulin. It is important to note that, during some of this time, Macleod was in his native Scotland. However, Macleod soon recognized that Banting and Best needed expert assistance and, in the fall of 1921, he recruited James Collip to the project, a scientist with prior experience in the isolation of bioactive molecules. Within a few short months, this team of scientists was successful in the purification of insulin to a sufficient extent that it could be used in humans with Type 1 (‘insulin deficient’) diabetes which, at that time, was a universally fatal disease.
On January 23, 1922, 14-year-old Leonard Thompson became the first patient ever to be successfully treated with insulin isolated from the pancreas of cattle, with apocryphal stories abounding of children being roused from their diabetes-induced comas with a single injection. Interestingly, the process for isolation of insulin was not originally patented, as Banting and Macleod felt that insulin should be freely available to all who were in need. Eventually, the University of Toronto bought the patent rights from Banting, Best and Collip for $1 and, in the spirit of the discoverers, licenced the technology to several companies in the USA and Europe so that people around the world could more rapidly benefit from what has been called ‘a cure from death’.
Insulin has indeed saved the lives of millions of people with Type 1 diabetes, and it is now also used in the treatment of many people with Type 2 (‘insulin resistant’) diabetes. However, its discovery also generated a substantial amount of acrimony. With the awarding of the Nobel Prize to Banting and Macleod, each of these investigators split their share of the Prize with another member of the team; Banting with Best, and Macleod with Collip. Although it could be argued that these other members of the team were equally deserving of the award, the Nobel Prize can only be awarded to a maximum of 3 individuals (with the exception of the Peace Prize which can be awarded to an organization). It was also argued that Best was ‘only a student at the time’, although history tells us that young people can indeed make essential contributions to scientific discovery (for example, 25-year-old William Lawrence Bragg who shared the 1915 Nobel Prize in Physics with his father, William Henry Bragg). However, throughout his life, Banting repeatedly asserted that Best deserved co-credit for the discovery, in particular as Macleod was not in Canada during the key summer months of 2021; Charles Best appears to have concurred with this opinion. In contrast, Macleod and Collip refused to comment on any part of the controversy, eventually leaving Toronto to pursue their careers at other institutions. In addition, many scientists prior to 1922/23 had attempted to isolate insulin albeit with limited success (including Minkowski, Zeuzler, Kleiner, Meltzer and Paulesco). Even though Banting was likely unaware of their contributions, given his general lack of knowledge of the scientific literature, many have expressed the opinion that one or more of these other investigators should also have shared in the Prize.
Many articles and books have now been written about the discovery of insulin, most notably The Discovery of Insulin by Michael Bliss. This momentous event in Canadian history has also been memorialized in the movie Glory Enough for All which is based on the book by Michael Bliss and features Canadian actor R.H. Thompson as Frederick Banting.
The true record of events in 1921-23 and beyond is now a matter of history. However, the legacy of this momentous discovery lives on in the lives of many other scientists. Indeed, a search of the Nobel Prize website reveals multiple references to insulin, either as a focus of the science or is cited as an inspiration for other discoveries:
- Physiology or Medicine 1947: Carl Cori and Gerty Cori “for their discovery of the course of the catalytic conversion of glycogen”, elucidated as part of their studies on the actions of insulin in the body.
- Chemistry 1955: Vincent du Vigneaud “for his work on biochemically important sulfur compounds, especially for the first synthesis of a polypeptide hormone”, which was the culmination of many studies on sulfur and insulin.
- Chemistry 1958: Frederick Sanger “for his work on the structure of proteins, especially that of insulin.”
- Chemistry 1964: Dorothy Hodgkin “for the determination of the structures of penicillin and vitamin B12”, work that was inspired by her studies on insulin.
- Physiology or Medicine 1977: Roger Guillemin and Andrew Schally “for their discoveries concerning the peptide hormone production of the brain”, most notably the hormone somatostatin which inhibits the release of insulin and Rosalyn Yalow “for the development of radioimmunoassays of peptide hormones” and especially the assay for insulin.
- Chemistry 1980: Paul Berg “for his fundamental studies of the biochemistry of nucleic acids, with particular regard to recombinant-DNA” and Walter Gilbert and Frederick Sanger “for their contributions concerning the determination of base sequences in nucleic acids”, which made possible the cloning of the human insulin gene and enabled the production of human insulin for clinical use.
- Chemistry 2009: Venkatraman Ramakrishnan, Thoms as Steitz and Ada Yonath “for studies of the structure and function of the ribosome”, a fundamental process that is essential for the biological synthesis of hormones such as insulin.
- Physiology or Medicine 2013: James Rothman, Randy Schekman and Thomas Südhof “for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells”, including proteins such as insulin.
Patricia Brubaker, Ph.D., F.R.S.C., is a Professor Emerita, Departments of Physiology and Medicine and a Banting & Best Distinguished Scholar at the University of Toronto, Toronto, ON Canada. Dr. Brubaker completed both her undergrad and PhD at McGill University.