This content originally appeared on diaTribe. Republished with permission.
By James S. Hirsch
The discovery of insulin promised a new age for an ancient condition but introduced unexpected challenges. James S. Hirsch explores the riveting history of this miracle drug on its 100th anniversary.
It was hailed as a miracle cure, a boon to the human race, an elixir that turned death into life and whose discovery was freighted with Biblical allusions. This year marks the one-hundredth anniversary of insulin, and the drug, first coaxed from the pancreas of dogs by unheralded scientists in a crude Canadian laboratory, remains one of the most remarkable feats in medical history.
But the history of insulin is not one of unalloyed celebration. It has moments of triumph as well as grievance. Like diabetes itself, it’s complicated.
It’s easy to lose sight of what insulin’s discovery represented in 1921. As the historian John Barry notes, the previous 2,500 years had seen virtually no progress in the treatment of patients, and the world had just emerged from the Spanish flu, which killed more than 50 million people and was ultimately subdued not by medical science but by the immune system’s adapting to the virus.
In other words, doctors in 1921 were all but impotent against any serious disease, including diabetes.
Then came insulin.
Anyone today who uses insulin does not need to be told of its life-saving power, and I am hardly an impartial observer, as it has kept me alive for the past 44 years.
Insulin today, however, bears little resemblance to what it was when I was diagnosed, let alone to what it was in its early decades. Patients then relied on imposing glass syringes whose thick needles had to be sharpened on whet stones and boiled for reuse. Nowadays, the ultrafine needles are disposable; smart insulin pens communicate with the cloud; and sleek insulin pumps are connected to continuous glucose meters. The insulin itself has been transformed – from impure concoctions derived from the smashed, blood-soaked pancreases of pigs or cows to laboratory-created, gene-splitting analogs with an array of pharmacokinetic properties. Inhalable insulin, long promised and finally delivered, represents a vaporous new-age alternative.
Research on insulin has attracted some of the world’s most brilliant scientists, as Nobel prizes have been given for insulin-related research in four separate decades. The work conducted on human insulin in the 1970s and ’80s, involving recombinant DNA, helped give birth to the modern biotechnology industry, including such pillars as Genentech and Biogen.
But there is more to this history than scientific breakthroughs and professional laurels.
Insulin has been misrepresented and misunderstood, even by some of its most important standard bearers, to the detriment of patients. For many years, the miraculous power of insulin, promoted in marketing efforts and publicity stunts, misled the public about the real-life experiences of those actually living with diabetes. In more recent years, insulin has been shunned by type 2 patients who could be using it or has been underused by type 1 patients. We are in the midst of a global diabetes epidemic, but insulin use has actually been declining because better therapies for type 2 diabetes have usurped insulin’s preeminence. And as insulin prices have soared, the insulin companies themselves, in a stunning reversal, have been transformed in some eyes from saviors to villains.
Meanwhile, the future of insulin itself is not certain, as better therapies could someday make obsolete the miracle drug of 1921.
Insulin was not technically “discovered” in 1921. Its role in the body was already known, its connection to diabetes already established.
The disease was first identified in 1500 BC, and in 250 BC, the disorder was named “diabetes” from the Greek word syphon, as its victims suffered from excessive urination. (One researcher later described diabetes as “the pissing evil.”) Researchers’ understanding of the disease advanced in 1869, when a German medical student named Paul Langerhans discovered “islands of cells” in the pancreas; and over the next three decades, investigators identified these cells as regulating glucose metabolism and directly associating them with diabetes. By 1916, the word “insulin” had been coined to describe that pancreatic substance.
But after more than 3,000 years, there was still no effective treatment for the disease. Researchers, however, did recognize that carbohydrates accelerated a patient’s decline, so the best treatment, developed in the early 1900s, was to withhold food – also known as the starvation diet, which allowed patients to extend their lives in sinister emaciation. Most of these patients were children, so grieving parents had to watch their children waste away – sometimes clustered together in hospital wards – and die either from starvation or diabetic ketoacidosis.
That made the search for insulin even more desperate, as investigators around the world sought to discover a “pancreatic extract” to save these dying children against the ravages of an ancient disease.
The breakthrough happened in Toronto in 1921, led by a prickly researcher who was a mere five years out of medical school. Frederick Banting had tried his hand as a surgeon but couldn’t earn a living, so he turned to teaching. He had no research experience and knew little about diabetes; but he had read a paper on it, and he later said that he had a dream about discovering insulin. In a longshot bid, Banting began his work in May at the University of Toronto, and he was assisted by a young medical student named Charles Best. They removed the pancreases from dogs to make them diabetic and then developed pancreatic extracts to try to lower the blood sugars. It was bloody, messy, difficult work – seven dogs died the first two weeks – but by August, one of the extracts, delivered by intravenous injections, proved successful. A biochemist, James Collip, was summoned to try to purify it for human use – he later called it “bathroom chemistry” – and on January 11, 1922, a 14-year-old boy, Leonard Thompson, received the first injection of insulin.
It was described as a “murky, light brown liquid containing much sediment,” it was given to him over several weeks, and it worked: the sugar and ketones in the boy’s urine disappeared.
“Diabetes, Dread Disease, Yields to New Gland Cure,” the New York Times announced.Tweet this“Diabetes, Dread Disease, Yields to New Gland Cure,” the New York Times announced.
The Toronto researchers couldn’t mass produce insulin, but Eli Lilly could, at least in the United States. (Other companies did in Europe.) Eli Lilly is headquartered in Indianapolis and, at the time, was in convenient proximity to many stockyards. The company stored a million pounds of frozen pancreases from pigs and cows to keep up with demand – there were an estimated one million Americans who needed insulin – and the company’s scientists, managers, and laborers were every bit the heroes as the Toronto researchers.
This new miracle drug did not disappoint.
Frederick Allen, one of America’s leading diabetologists, said his patients, upon receiving insulin, “looked like an old Flemish painter’s depiction of a resurrection after famine. It was a resurrection, a crawling stirring, as of some vague springtime.”
Elliott Joslin, America’s preeminent diabetes clinician, described his patients who took insulin as the “erstwhile dead” and invoked Ezekiel’s vision of the valley of the dry bones, in which God says, “Come from the four winds, O breath, and breathe upon these slain, that they may live.”
The photographs told an even more dramatic story: In one famous picture, a naked 3-year-old boy who weighs 15 pounds clings to his mother, his face grimacing, his ribs exposed. After taking insulin for only three months, a head shot shows the boy with full cheeks, alert brown eyes, and dark locks of hair. He looks normal – and cured.
If there were any doubt about insulin’s curative powers, Elizabeth Evans Hughes removed them. Her father, Charles Evans Hughes, had been the governor of New York, a justice on the U.S. Supreme Court, a candidate for president, and in 1922, was the U.S. Secretary of State. Elizabeth had been diagnosed with diabetes in 1919, so when she took her first dose of insulin in 1922, she became the poster child for this new drug.
After more than three millennia, it appeared that medical science had defeated diabetes.Tweet this“Hughes’ Daughter ‘Cured’ of Diabetes” declared one unidentified newspaper. After more than three millennia, it appeared that medical science had defeated diabetes.
Stay tuned for parts two and three of this riveting story over the next two weeks!
I want to acknowledge the following people who helped me with this article: Dr. Mark Atkinson, Dr. David Harlan, Dr. Irl Hirsch, Dr. David Nathan, Dr. Jay Skyler, and Dr. Bernard Zinman. Some material in this article came from my book, “Cheating Destiny: Living with Diabetes.”
James S. Hirsch, a former reporter for The New York Times and The Wall Street Journal, is a best-selling author who has written 10 nonfiction books. They include biographies of Willie Mays and Rubin “Hurricane” Carter; an investigation into the Tulsa race riot of 1921; and an examination of our diabetes epidemic. Hirsch has an undergraduate degree from the University of Missouri School of Journalism and a graduate degree from the LBJ School of Public Policy at the University of Texas. He lives in the Boston area with his wife, Sheryl, and they have two children, Amanda and Garrett. Jim has worked as a senior editor and columnist for diaTribe since 2006.