How a disinformation campaign wiped out synthetic insulin’s deadly effects
Hundreds of people died in the two decades after synthetic insulin was launched. A disinformation campaign covered up their plight
- Text by Audrey Farley
- Header Photo by Novo Nordisk
In 1994, eight-year-old Zoe Burbridge went to bed in the town of Northampton, England, and never woke up. In 2002, 15-year-old Selina Trapp, from Derby, also in the United Kingdom, died in her sleep. Two years earlier, an American, 49-year-old Susan Mescher from Lexington, Michigan, had slumped over in the shower, never to regain consciousness.
These individuals were just a few of the hundreds of diabetics who suddenly died between 1983 and 2002. Medical examiners attributed their deaths to complications related to the condition, such as cardiovascular problems, but they all had something else in common at the time of death: every one of them had recently switched from animal to genetically engineered insulin.
Since the development of insulin therapy in the early 1920s, more than half a century after the initial discovery of the hormone, diabetics had used porcine or bovine insulin made by multinationals Eli Lilly or Novo Nordisk, or domestic companies. These formulas were generally safe and effective, but could not be manufactured on a mass scale.
Determined to capture a global market at a time when worldwide insulin sales—which stood in 1982 at $400 million—were expected to double, both Eli Lilly and Novo Nordisk invested in biotechnological production. By altering Escherichia coli bacteria with recombinant DNA methods or modifying one amino acid contained in pig-derived insulin, Eli Lilly and Novo Nordisk, respectively, could mass-produce insulin and eliminate smaller manufacturers. These methods enabled each company to produce biosynthetic “human” insulin—and market it as such, at a much higher price.
In the U.S., in 1983, animal insulin cost about 28 cents daily, while human insulin cost about 53 cents. Furthermore, once the technology was in place, manufacturers could use it to mass produce other drugs, such as human growth hormones. Manufacturers’ profits were set to explode.
At the urging of their doctors, hundreds of thousands began to adopt biosynthetic insulins over the next decade and a half.
However, during this time, thousands of diabetics and their relatives began to report adverse effects ranging from memory trouble to what became known as “dead in bed” syndrome. Individuals in Canada, the UK, and the U.S. attempted to organize legal actions, which were eagerly reported by the media. “Change from animal to human insulin raises questions,” Eli Lilly’s hometown newspaper, The Indianapolis Star, headlined a story in 1989. “Diabetes Deaths and Human Insulin,” The Guardian reported another that year. Regulatory agencies, such as the U.S.’s Food & Drug Administration (FDA) and the UK’s Committee on the Safety of Medicines, agreed to hear evidence from researchers, while publicly maintaining there was no reason for alarm.
Having thrown vast amounts of resources into investing in biotechnology, Eli Lilly and Novo Nordisk took steps to silence those reporting harms. They hired PR firms to discredit suffering individuals, planted op-eds in newspapers, funded clinical studies promoting biosynthetic insulin and even developed a video game.
Novo Nordisk did not respond to requests for comment from Coda Story.
In the anti-vax era, skeptical consumers have spread much online disinformation about drugs. The story of biosynthetic insulin’s introduction reminds that, before the digital age, sections of the drug industry and media caused widespread harm by promoting what is now often described as “fake news.”
Dr. Warren Bell, a general practitioner in Salmon Arm, British Columbia, recalls the “Kool-Aid story” of how biosynthetics were going to revolutionize diabetes treatment. “No one questioned the narrative that ‘human’ insulin was superior,” Bell explained in an interview with Coda. “We were all swept up in the PR frenzy.”
But the consequences were enormous. Not only did the introduction of biosynthetic human insulin cause widespread harm, it restricted access to animal insulins and—with the entry of the French pharmaceutical company Sanofi in 2000—paved the way for three manufacturers to dominate the world market.
This outcome has proved disastrous for diabetics in low- and high-income countries alike.
Because the driving force behind human insulin was profit and not improved therapy, manufacturers had to distort justification of need for the product. They warned of an impending shortage of cattle pancreta, from which animal insulin was derived, due to the increasing diabetic population. Many doubted this warning, especially after the U.S. Federal Trade Commission scolded Eli Lilly for conspiring with foreign and domestic firms to fix prices for pancreata, suggesting that the company’s motives lay in the promotion of its new product.
The two manufacturers also claimed—without solid evidence—that fewer individuals would have allergic reactions to the newer insulin species. Appealing to very human fears, Eli Lilly’s Vice President of Research Irving Johnson asked a reporter from the Financial Times, “Which would you like to inject something that’s human, or something from a pig?”
Regulators were so enthralled by the idea of biosynthetic insulin that they failed to conduct a thorough review. The U.S. FDA approved Eli Lilly’s Humulin within four months, despite admitting that the drug did not improve upon animal-derived insulin.
The FDA’s approval was based on trials conducted on fewer than 400 participants in less than 18 months, in contrast to the far larger sample groups and the usual 40-to-60 month average period required for testing compounds or treatments.
After seven participants withdrew, Solomon Sobel, an FDA medical officer, requested an investigation. These participants might have withdrawn due to hypoglycemia, as three participants in a Novo Nordisk clinical study had. But no inquiry was ever conducted, leaving their motivations unclear. According to Henry Miller, head of the examination team, Sobel had also expressed reluctance about approving the product in such a short time. So Miller, a junior colleague, waited until Sobel was on vacation to take Humulin to another supervisor to be rubber-stamped. Miller does not regret backdooring human insulin. For him, the drug was epochal, and he’s proud to be part of its story.
European and Canadian regulators also approved biosynthetic insulin without substantial evidence of positive outcomes.
The media was equally commending in its praise. One news agency observed that diabetics were “making medical history” by using human insulin. Meanwhile, the Los Angeles Times lauded the “major breakthrough,” and The New York Times quoted Miller on the scientific advance for recombinant DNA techniques, “We have come of age.”
Casualties and disinformation
For many, this alleged “breakthrough” was a nightmare. Shortly after beginning to take human insulin on the medical advice that animal insulins would soon be obsolete, thousands of diabetics experienced a loss of the warning signs that usually precede episodes of hypoglycemia (low blood glucose), such as shakiness, sweating, and palpitations. These warning signals allow diabetics to intervene (consume sugar) before their blood glucose drops too low, causing fainting, seizures, or even death. The loss of warning signals was especially problematic considering that biosynthetic insulin acted more sharply and unpredictably than animal insulins.
Nineteen-year-old Kristine Spanks in British Columbia lost her warning signals after switching to biosynthetic insulin in 1998. “She’d be talking, and then she’d just collapse,” her mother, Maureen Schug, recalls. “She’d be too far gone to sip juice. We’d rub sugar on her gums.” One day, after a period of prolonged unconsciousness, Spanks sustained severe brain damage from which eventually died. According to her mother, she anticipated such a tragedy: “She lived in fear. She was always afraid of the next blackout.”
So was Chris Ferguson, another British Columbian who died while taking human insulin. Shortly before his death in 1996, the seventeen-year-old athlete told friends that he feared he would not live much longer. Since transitioning to human insulin, he, too, experienced uncontrollable drops in blood sugar, as well as chronic muscle and joint pain. Other users reported memory loss, aggressive tendencies, and uncontrollably high glucose, leading to diabetic ketoacidosis (acid build-up in the blood).
Manufacturers were well aware of human insulin’s reported dangers; but instead of addressing them, they embarked upon campaigns to discredit and even assassinate the character of those struggling to manage their diabetes with biosynthetic insulin.
However, manufacturers’ greatest resource of disinformation was industry-funded organizations.
Between 1986 and 1989, the British Diabetes Association (BDA), now known as Diabetes UK, had received over 3,000 letters citing adverse reactions. At first, the organization, hired an independent researcher named Natasha Posner to assess the risks posed by biosynthetic insulin. The BDA promised to publish Posner’s full report, which concluded that 10% of users had experienced dangerous side-effects while using biosynthetic insulin and that the problems often disappeared when they returned to animal insulin.
Yet, in 1993, the BDA elected not to publish the report. It was “too alarmist,” BDA official Simon O’Neill told The Guardian in 1999, when the report was leaked. Posner’s report quoted individuals who had lost jobs, crashed vehicles, divorced spouses, or generally reported that life was “absolute hell” on human insulin. The BDA sponsored an ad in The Observer in 1995, condemning those who “unnecessarily caused distress,” such as whistleblower Matthew Kiln—a doctor and diabetic who had demanded government action on biosynthetic insulin—and the 700 individuals organizing a group litigation.
In a statement, Simon O’Neill, Diabetes UK’s Director of Health Intelligence and Professional Liaison, said the report recommended that anyone experiencing severe hypoglycemia following transition should discuss the issue with their healthcare providers. “The research we commissioned in the early 90’s found that problems with severe hypoglycemia following transition from animal to human insulin were being experienced by a minority of people, and as such we took—and stand by—the decision to produce and publish a balanced report reflecting this fact. Our advice to people living with and affected by diabetes has always been, and remains, based on the best evidence available to us at the time.”
In the U.S. and Canada, where class action suits were being launched, the American Diabetes Association (ADA) and Canadian Diabetes Association (now Diabetes Canada) also defended biosynthetic insulin, referring to individuals who had spoken out about its harmful effects as “emotional.” The stances of these trusted organizations largely explain why the class actions failed and U.S. regulators never conducted post-market surveillance, accepting Eli Lilly’s offer to revise the warning label to note the risk of hypoglycemia unawareness. Regulators in the U.S., Canada, and the UK were also satisfied with the claims of manufacturers that all insulins presented hypoglycemic risk, even though awareness of the condition was common prior to the introduction of biosynthetic insulins.
The revised label on Eli Lilly’s Humulin read, “a few patients who experienced hypoglycemic reactions after being transferred to Humulin have reported that these early warning symptoms were less pronounced than they were with animal-source insulin.” This implied that the loss of hypoglycemia warning signals was not caused by the use of biosynthetic human insulin, but by switching from animal insulin. With this, the company implicitly demanded that providers prescribe biosynthetic human insulin to newly diagnosed patients. Providers complied.
Aftermath and market consolidation
In the late 1990s and early 2000s, when human insulin was going off-patent, Eli Lilly and Novo Nordisk introduced “analog” insulins. Though also made from recombinant technology, analogs are different at a molecular level, and many individuals cite markedly improved quality of life with their use. Nathan Loewy, 31, of Winthrop, Minnesota, spent his childhood in and out of hospitals while using human insulin. However, he claims that his life was transformed within a year of transitioning to analogs in 2001. “I noticed increased control and fewer extreme highs and lows.”
Still, Loewy eventually developed neuropathy, chest pain, muscle pain, retinopathy, and other complications of diabetes, which he attributes to “the lack of control [he] had for greater than one decade” while using human insulin. He never used animal-derived insulin.
While Loewy is satisfied with analogs, some, like 76-year-old Brent Hoadley from Lamont, Florida, yearn for the now-withdrawn animal-sourced products. Hoadley resents having to continuously wear a glucose monitor and insulin pump to detect hypoglycemia and stabilize his glucose levels. “They keep entrapping us with more and more equipment, since they’ve taken away an insulin that worked.”
With biosynthetic insulin, Eli Lilly and Novo Nordisk established a global market within which small producers can no longer compete. Diabetics worldwide rely upon three primary manufacturers, which have neglected geographic regions perceived less profitable due to market size or price controls, leaving half of the 100 million insulin-dependent diabetics worldwide without access to any type of treatment. This oligopoly accounts for the $300-a-vial cost of analogs in the U.S., where Eli Lilly, Sanofi, and Novo Nordisk are accused of price-fixing and paying manufacturers not to produce biosimilar (generic) insulin. Due to costs, one in four diabetics admit to under-dosing, and dozens have died doing so.
Rather than taking measures to curtail costs, U.S. lawmakers have touted cheaper human insulin as a solution. So have manufacturers, industry-funded physicians, and ADA representatives. While some can safely use human insulin, others cannot.
Despite the hardships endured by its users, biosynthetic human insulin is hailed as one of the greatest medical marvels of the century. In 2000, the British Prime Minister Tony Blair cited it as an example of biotechnology’s promise to produce “life-saving medicines”. The Smithsonian Museum of American History hosts a collection titled the “Birth of Biotech,” which celebrates human insulin as the quintessence of the “inventive thinking” that has advanced civilization. The stories of those whose lives have been ruined or lost to it have been mostly erased.
Insulin manufacturers are not the only parties to highlight the innovative nature of their products, in order to distract from risks and protect their revenues. Many drug makers tweak products and frequently talk of newer, improved therapies in the pipeline in order to defend drug costs.
But there is no reason to presume that treatments in the making will necessarily improve upon those that already exist, nor that existing treatments will remain available for those who need them. Dr. Warren Bell knows this. “Whenever a drug like human insulin is commercially successful, instead of diversity, you get complete effacement of prior alternatives,” he said. “So anyone who does better with older treatments is immediately marginalized.”
That is precisely what happened for many of his patients.
Additional research by Colleen Fuller.