In the latest episode of "Acquired," hosts Ben Gilbert and David Rosenthal traverse the history of insulin, from its discovery to modern-day innovations that have the power to change lives. The episode begins with a look back at the monumental discovery of insulin by researchers in Toronto in 1921—a breakthrough that turned a once-fatal disease into something manageable, and unfolds the narrative of how insulin's history is punctured with controversy and triumph.
The hosts detail the evolution of insulin production and how World War II affected companies like Nordisk and Novo, leading to the genetics and biotech revolution incited by Genentech's synthetic "human" insulin in 1980. The story continues to trace the escalation of the global diabetes epidemic, drawing connections between rising obesity rates and the growing demand for insulin. The episode zeroes in on the impact of GLP-1 drugs developed by Novo Nordisk and investigates the challenges in the U.S. healthcare system that could hamper patient access to these potential life-altering treatments. Join Gilbert and Rosenthal as they explore how these medical advancements from Novo Nordisk might not only revolutionize diabetes care but also alter the company's course in tackling global health crises.
Sign up for Shortform to access the whole episode summary along with additional materials like counterarguments and context.
In 1921, Frederick Banting, Charles Best, and John McLeod made the life-altering discovery of insulin at the University of Toronto. This critical development transformed diabetes from a fatal diagnosis to a manageable condition, despite a problematic delivery method that required frequent dosing. The discovery earned Banting and McLeod the Nobel Prize in Physiology or Medicine in 1923, but not without controversy over their apportionment of credit; many believed Banting and Best deserved the majority recognition. Regardless, their achievement remains a testament to the influence that medical breakthroughs can have on humanity.
In 1923, Copenhagen saw the birth of Nordisk when August Crowe, Marie Crowe, and H.C. Hagadorn produced insulin based on the Toronto method. Their enterprise evolved, thanks to Hagedorn's vision, into a foundation-owned institution with a goal of making insulin accessible and funding diabetes research. August and Marie Crowe obtained rights from John McLeod for Scandinavian distribution, a move crucial to Nordisk's success. Although Nordisk and Novo, founded by the Peterson brothers post-termination by Nordisk, would engage in a 65-year rivalry, this competition drove significant innovations in the insulin industry, such as Novo's liquid insulin and Nordisk's insulin pen development.
World War II ushered in challenges for Nordisk and Novo in occupied Denmark. Nordisk's strategic reliance on international licensing revenue was disrupted during the Nazi occupation, notably affecting their market presence. Meanwhile, Novo capitalized on their European operations to become the primary insulin supplier amidst Nazi occupation. This wartime strategy allowed Novo to surpass Nordisk in size and market influence after the war, necessitating a strategic comeback by Nordisk once the conflict ended.
Genentech, in collaboration with Eli Lilly, dramatically altered the landscape of medicine in 1980 by announcing their development of biosynthetic "human" insulin. This advancement, stemming from recombinant DNA technology, enabled the treatment of many more people with type 2 diabetes, as insulin was no longer limited to being extracted from animal sources. Their IPO reflected the massive potential and marked a significant turning point in biotechnology, inspiring further investments and innovations in the field.
The surge in obesity and type 2 diabetes globally has greatly expanded the market for insulin manufacturers. The higher incidence of these conditions due to lifestyle and dietary changes has increased demand for insulin, necessary to regulate high blood sugar. However, this growth has also highlighted issues like insulin cost and the necessity of public health initiatives to counteract the underlying causes of diabetes and improve the health of the population.
Lotte Dinesen's pioneering work led to the creation of GLP-1 drugs such as liraglutide and semaglutide. These drugs, which reduce appetite and food intake, faced internal skepticism at Novo Nordisk but eventually proved successful for both diabetes and weight loss treatment. Despite significant industry hesitation and challenging deadlines, Dinesen's team persevered, revealing that competitive drive and determined focus on long-term research can yield revolutionary treatments for widespread health issues.
The popularity of GLP-1 drugs Ozempic and Wegovy has been overwhelming, with demand outstripping supply and significantly boosting Novo Nordisk's revenue. These drugs have shown promise in treating not only diabetes but also cardiovascular disease and Alzheimer's. Despite their success, issues of price, insurance coverage, and access possess significant challenges in the U.S. healthcare system, with many patients facing high out-of-pocket costs for these treatments. The high demand and the significant market potential for these drugs point to a notable shift in Novo Nordisk's role in not only diabetes treatment but also in addressing the global obesity epidemic.
1-Page Summary
In the pivotal year of 1921, the hormone insulin was a groundbreaking discovery at the University of Toronto Medical School by a team including physician Frederick Banting, his assistant Charles Best, assistant medical school dean John McLeod, and chemist James Collip. This momentous breakthrough has significantly altered the management of diabetes.
August Crowe, a previous Nobel laureate and founder of what would become Novo Nordisk, recognized the monumental impact of this medical advancement. Consequently, he nominated Banting and McLeod for the Nobel Prize. In 1923, Banting and McLeod were awarded the Nobel Prize in Physiology or Medicine, though there were historical contentions concerning the apportionment of credit for the discovery. Many believe that Banting and Best contributed the majority of the work in isolating insulin.
Despite the disputes, what stands uncontested is the scientific miracle that unfolded. Prior to this discovery, individuals diagnosed with type 1 diabetes faced a grim prognosis, with the only respite being a starvation diet that, at best, only briefly extended life. The signific ...
The discovery of insulin by Banting, Best, and McLeod at the University of Toronto in 1921
In Copenhagen in 1923, a significant development occurred when August Crowe, Marie Crowe, and H.C. Hagadorn utilized the Toronto method to extract insulin, marking the first time insulin was produced in Scandinavia and potentially continental Europe. Realizing the process they used would not scale sufficiently, they partnered with August Kongsted of the Lion Chemical Factory to increase production. By the summer of 1923, they successfully completed trials with eight human patients.
Recognizing the growing demand for Insulin Leo—produced by Nordisk, and the first of its kind in continental Europe—in 1924, Crowe, Hagedorn, and Kongsted established an independent institution to produce and distribute insulin across Europe. This institution was an operating company wholly owned by a foundation, influencing Nordisk's development and market strategies significantly.
August and Marie Crowe learned of insulin's discovery in Toronto and resolved to visit John McLeod's lab. Upon arriving in America, they were motivated to contact McLeod to understand insulin production and secure rights for distribution in Denmark for Hagedorn. McLeod allowed August Crowe to observe the insulin production process and facilitated the founders' rights for distribution throughout Scandinavia, similar to a deal with Eli Lilly for North America.
While details on the creation of Nordisk Insulin as a foundation-owned institution are not explicitly provided, it is clear from the narrative that the founders intended to make insulin accessible. It was August Crowe and Hagedorn who were at the helm of this enterprise, with Crowe and Hagedorn being members of the board and Hagedorn managing the day-to-day operations.
The foundation owning Nordisk had a dual mission: to sell insulin at cost in Scandinavia for maximum public health benefit while exporting at market prices elsewhere to fund diabetes research and development. Profits from exports were used by the foundation for grants and diabetes-related research, supporting diabetes patients in Scandinavia. Importantly, the foundation controls a significant portion of the voting shares and economic shares of Novo Nordisk.
After being fired from Nordisk, the Peterson brothers went on to found their company, Novo, which would eventually lead to a staunch rivalry with Nordisk. They develo ...
Nordisk's founding by August Crowe, Marie Crowe, and H.C. Hagadorn in Copenhagen in 1923
...
World War II significantly impacted the operations and strategic dynamics of Nordisk and Novo, two insulin producers, as they navigated through the Nazi occupation of Denmark and the larger conflict enveloping Europe.
As the war unfolded, Nordisk found itself in a difficult position. The company, which had previously based its strategy on licensing internationally, particularly to allied countries, found this avenue no longer viable after the Nazi occupation of Denmark. The infighting between Nordisk and Novo became less relevant as Nordisk went into a figurative hibernation. With the invasion, the company could no longer receive payments from its international licensees because the transfer of funds from allied countries was blocked.
In contrast to Nordisk's struggles, Novo was better positioned during the wartime period. The company had been scaling up their insulin production throughout Scandinavia and Europe. This preparation allowed Novo to become the main insulin supplier in Nazi-occupied Europe following the German invasion. With the licensing restrictions imposed on Nordisk, Novo's operations and influence expanded without facing competitio ...
The effects of World War II on Nordisk and Novo's insulin production
Ben Gilbert and David Rosenthal elaborate on how biotechnology company Genentech marked a pivotal moment in drug development, introducing methods that scaled up production and accessibility of vital medicines like insulin.
Genentech, much like other legendary Silicon Valley startups such as Google and Facebook, made a historical impact with their landmark announcement in 1980, according to Gilbert and Rosenthal. The company, in partnership with Eli Lilly, announced that they were working on developing biosynthetic "human" insulin. This endeavor was a monumental step forward and is regarded as one of Silicon Valley’s most significant contributions.
The groundbreaking work of Genentech not only exemplified innovation but also attracted immense investor interest. Their public offering in the fall of 1980 became the largest venture-backed initial public offering (IPO) to date, reflecting the high expectations for the biotech industry.
The podcast touches on the implications of Genentech's advancements for type 2 diabetes treatment. Prior to the advent of recombinant DNA technology, a method developed by Genentech, the treatment of type 2 diabetes rarely involved insulin, mainly due to the limited supply t ...
The genetics and biotech revolution kickstarted by Genentech in 1980
The global increase in obesity and type 2 diabetes rates has resulted in substantial growth for companies producing insulin. As these health issues become more prevalent, demand for diabetes management products, especially insulin, is on the rise.
In recent years, obesity has surged worldwide due to sedentary lifestyles, high-calorie diets, and urbanization, leading to a higher incidence of type 2 diabetes. This chronic condition occurs when the body either resists the effects of insulin—a hormone regulating the movement of sugar into cells—or doesn't produce enough insulin to maintain a normal glucose level.
As more individuals are diagnosed with diabetes, insulin manufacturers are seeing an unprecedented demand for their products. Insulin is vital for people with type 2 diabetes since it helps mitigate the complications associated with high blood sugar levels. The market for insulin and related diabetic care is expanding as patients require ongoing treatment.
Unfortun ...
The rise in obesity and type 2 diabetes leading to huge growth for insulin companies
Lotte Dinesen and her team at Novo Nordisk embarked on a groundbreaking journey that spanned over two decades to develop GLP-1 drugs like liraglutide and semaglutide, which have since transformed the treatment of type 2 diabetes and obesity.
Research into GLP-1 drugs started in the early '90s based on the discovery of GLP-1's significant role in insulin production for type 2 diabetes patients. Dinesen began her career at Novo Nordisk in 1989, later shifting from the enzyme division to tackle diabetes treatment within the diabetes business unit in the early to mid-1990s.
The earliest indications that GLP-1 drugs could reduce appetite came from animal trials where rats would stop eating when injected with high doses of liraglutide, sometimes to the point of starvation. This appetite-reducing effect carried over to human trials, though not to the same extreme degree. Such drugs work by signaling satiety to the brain and slowing the digestive process, ultimately leading to reduced food intake.
Dinesen's work faced pressures internally, as Novo Nordisk management was skeptical of the viability of GLP-1 drugs. They gave Dinesen an ultimatum: find a successful drug candidate within a year or have the program shut down. This skepticism mirrored the industry's hesitation towards developing weight loss drugs, which historically had been plagued with concerns over safety and effectiveness.
Despite challenges, Dinesen's team continued their research and development efforts, leading to the creation of liraglutide—a GLP-1 analog with a longer half-life in the human body, thanks to the addition of a fatty acid to the molecule. After successful trials, Novo Nordisk was able to beat competitors like Eli Lilly to market with this innovative treatment for type 2 diabetes.
The path to r ...
The development of GLP-1 drugs like liraglutide and semaglutide by Novo Nordisk scientist Lotte Dinesen
...
GLP-1 agonist drugs such as Ozempic and Wegovy, marketed by Novo Nordisk, have shown massive consumer demand, leading to supply shortages and highlighting questions around insurance coverage and access.
David Rosenthal and other commentators discuss the impact of GLP-1 drugs on the market, particularly focusing on the rapid demand for Ozempic and Wegovy. Novo Nordisk's revenue is significantly bolstered by diabetes-focused GLP-1 drugs (51%) and obesity-related GLP-1 drugs (18%), with semaglutide and liraglutide being the main sources of this revenue. Semaglutide's long half-life and potential to treat other conditions like cardiovascular disease and Alzheimer's indicates an extended activity beneficial for various organs.
Ozempic was highly successful upon its launch, earning over a billion dollars in revenue in its first year, despite being supply constrained. The demand for Ozempic and Wegovy continues to surpass available supply, a challenge that Novo Nordisk anticipates will persist. After FDA approval, Wegovy saw more prescriptions in just over a month than Saxenda had during its entire lifespan, and supplies for both drugs were fully exhausted due to this high demand. The market is seeing a "catch up race" among pharmaceutical companies to develop GLP-1 drugs to meet significant consumer demand.
The high sticker price of GLP-1 drugs like Ozempic and Wegovy raises issues around insurance coverage and access in the United States. Ozempic costs over $1,000 per month and Wegovy over $1,300 per month before insurance, with stark pricing contrasts in countries like Canada and the UK.
Discussing how these drugs are paid for in the United States brings up disparities between individuals who can afford to pay out-of-pocket and those relying on private insurance. There is a ...
The potential for GLP-1 drugs like Ozempic and Wegovy to treat obesity and transform Novo Nordisk
Download the Shortform Chrome extension for your browser