The Insulin Story: Part 2 - Mass-Producing Insulin and the MaRS Innovation Legacy
When Frederick Banting, Charles Best, J.B. Collip and J.J.R. Macleod publicized their discovery of insulin in March 1922, a flurry of public and media attention immediately followed. However, praise from the medical community was not yet unreserved. Other researchers had, by similar approaches, isolated extracts that proved irreparably toxic, thus the Toronto group’s findings were met with a certain degree of scepticism. If insulin were to have any clinical value, it still remained to be seen whether it could be mass-produced in a non-toxic form of standardized potency. This task was initially assigned to the University of Toronto’s Connaught Laboratories, under Collip’s direction. But Collip suddenly became unable to produce large batches of decent potency, then, alarmingly, not even small ones by his old method. Collip frantically searched for the defect that had crept into in his method as diabetics formerly receiving treatment teetered on the brink of death and one patient did die. Production was finally restored two months later, but it had become clear that the demands of further developing insulin had exceeded the resources of the University of Toronto-Toronto General Hospital collaboration. Moreover, outstanding issues remained in producing insulin of consistent potency.
A committee was struck by three University of Toronto board members, the four discoverers and the director of Connaught Laboratories. Named the Insulin Committee (IC), it was responsible for managing the problems dealing with patenting, financing and controlling the quality of mass-produced insulin (read commercialization). The committee quickly licensed production rights to Eli Lilly and Company of Indianapolis, a respected pharmaceutical firm with experience in standardizing glandular extracts. The agreement, essentially, was to pool the institutions’ resources. In return for exclusive production rights in the United States, Lilly was obliged to disclose to the IC any improvements it made to the production process and vice versa. Lilly proved a very useful partner: by October, purity and stability had improved by a factor of one hundred and variability in lot-to-lot potency had decreased from 25% to 10%.
The network was quickly widened with the global emergence of similar institutions for developing and distributing insulin. In an act of colonial deference, one of the IC’s first acts was to hand over development rights to Britain’s Medical Research Council. In November, the eminent Danish researcher August Krogh visited Toronto and toured the insulin operation’s facilities. Upon returning, he was authorized to bring insulin to Scandinavia, establishing a not-for-profit ‘Nordisk Insulinlaboratorium.’ Encouraged by Banting, chief of insulin’s clinical development, universities, hospitals, researchers and clinicians worldwide also began to share their insights and observations. Even patients using insulin would write with their comments. In the case of one particularly prolific patient, Banting was told “This last lot has been the best I’ve ever had with the exception of no 103…” and later, “I have reason to believe that the last batch you sent has greatly deteriorated.” Thanks to this broad and lively collaborative network, Insulin was developed astonishingly quickly. After the discoverers’ published their first results in March 1922, insulin was rendered suitable for mass-production by the end of 1923 and “perfected” within the next year.
The Heritage Building is much more than a historic physical space. It represents the prestigious lineage of medical discoveries that were developed on site as well as a high international standard of research excellence. But this legacy is not merely quantitative; it is qualitative as well. From the 1906 Hospital Act to the refinement of Insulin in 1924, the Hospital’s early history reflects innovation in the innovation paradigm itself.
The Toronto group was not the first to work on insulin; scientists in the United States, Germany and Romania had started much earlier along similar lines of research. In fact, historian Michael Bliss suggests that if it hadn’t been for the Banting group, insulin might have been discovered as soon as five months later than it was. The Toronto group prevailed thanks to its great access to resources, both material (dogs, laboratory equipment, etc.) in the early stages and intellectual (e.g. Eli Lilly know-how) later on. Both these assets were available thanks to the collaborative, trans-institutional, trans-sectoral relationships the Hospital established with the University, its international counterparts, the private sector and the general public.
This collaborative model of innovation is MaRS’ true legacy. Not only did it bring one of modern medicine’s greatest triumphs to Toronto, it offers a similarly brilliant prospect for present research. Indeed, MaRS’ doctrine of Convergence Innovation, bringing together the communities of research, business and capital, is a continuation and extension of this historical theme. Banting was a surgeon by training, but was inspired by an endocrinology article—a random collision of medical disciplines. His insight was nurtured and advanced by wide-ranging personal and institutional relationships. Likewise, MaRS’ philosophy of building relationships and encouraging collisions—particularly those cutting across academic and vocational divides—seeks to create an environment that breeds inspiration and provides the infrastructure to see that inspiration realized.
A committee was struck by three University of Toronto board members, the four discoverers and the director of Connaught Laboratories. Named the Insulin Committee (IC), it was responsible for managing the problems dealing with patenting, financing and controlling the quality of mass-produced insulin (read commercialization). The committee quickly licensed production rights to Eli Lilly and Company of Indianapolis, a respected pharmaceutical firm with experience in standardizing glandular extracts. The agreement, essentially, was to pool the institutions’ resources. In return for exclusive production rights in the United States, Lilly was obliged to disclose to the IC any improvements it made to the production process and vice versa. Lilly proved a very useful partner: by October, purity and stability had improved by a factor of one hundred and variability in lot-to-lot potency had decreased from 25% to 10%.
Denmark’s August Krogh, also a Nobel laureate in Medicine (1920).
RETURNING TO THE PRESENT: MARS’ INNOVATION LEGACY
The Heritage Building is much more than a historic physical space. It represents the prestigious lineage of medical discoveries that were developed on site as well as a high international standard of research excellence. But this legacy is not merely quantitative; it is qualitative as well. From the 1906 Hospital Act to the refinement of Insulin in 1924, the Hospital’s early history reflects innovation in the innovation paradigm itself. The Toronto group was not the first to work on insulin; scientists in the United States, Germany and Romania had started much earlier along similar lines of research. In fact, historian Michael Bliss suggests that if it hadn’t been for the Banting group, insulin might have been discovered as soon as five months later than it was. The Toronto group prevailed thanks to its great access to resources, both material (dogs, laboratory equipment, etc.) in the early stages and intellectual (e.g. Eli Lilly know-how) later on. Both these assets were available thanks to the collaborative, trans-institutional, trans-sectoral relationships the Hospital established with the University, its international counterparts, the private sector and the general public.
This collaborative model of innovation is MaRS’ true legacy. Not only did it bring one of modern medicine’s greatest triumphs to Toronto, it offers a similarly brilliant prospect for present research. Indeed, MaRS’ doctrine of Convergence Innovation, bringing together the communities of research, business and capital, is a continuation and extension of this historical theme. Banting was a surgeon by training, but was inspired by an endocrinology article—a random collision of medical disciplines. His insight was nurtured and advanced by wide-ranging personal and institutional relationships. Likewise, MaRS’ philosophy of building relationships and encouraging collisions—particularly those cutting across academic and vocational divides—seeks to create an environment that breeds inspiration and provides the infrastructure to see that inspiration realized.