The Weekly Dose: Insulin's second coming
In the wake of Biocon Pharma’s announcement that it will supply insulin to patients in low- and middle-income countries at just seven rupees a day, here is a short history of insulin, and its status in India today.
A century ago, if you were born with diabetes, you could not expect to live beyond adolescence. If you developed it as an adult, calorie control and weight loss were the only forms of treatment, not the adjunct lifestyle changes they are today. The symptoms of chronic diabetes had never even been observed; few people survived long enough to exhibit them. Diabetes has no cure, but it can be controlled; in less than a hundred years, we have gone from having no anti-diabetic drugs to mass-producing a soon-to-be universally affordable one, jump-started by the discovery of a wonder medicine - insulin.
Long before this, we had understood diabetes. We knew the pancreas had something to do with it but weren’t sure what. The pancreas only secreted enzymes that helped with digestion; what was this other mysterious substance that controlled blood sugar levels?
An unlikely researcher
In 1920, Frederick Banting was a Canadian orthopaedic surgeon stuck in an unsuccessful practice after having served in the First World War. To make ends meet, he became a part-time physiology teacher at a medical school. While preparing for a lecture on the pancreas, he came across a research paper that would alter the course of his life, and many of ours.
Scientists knew that the pancreas produces both digestive enzymes and insulin, but couldn’t physically separate the latter from the former. Banting’s reading gave him his eureka moment: why not tie off the duct that pours the enzymes into the digestive tract? This would lead to the degeneration of the pancreatic cells producing the enzymes, leaving behind only those pockets which produce insulin. Aha!
Banting had no advanced degree, no research experience and no published papers. Later, he was to admit that had he been thoroughly acquainted with all the work done in this field before him, he might never even have begun his. But he was 29 years old, passionate, and convinced of his hypothesis; he shared his idea with James Macleod, the head of the physiology department at the University of Toronto, who was sceptical both of the man and his proposal. However, Macleod gave Banting the use of his lab, ten laboratory dogs and two student assistants, who flipped a coin to decide who would work with Banting in the first half of the summer break; the man who won was 22-year-old Charles Best, with whom Banting shared his half of the prize money from the Nobel Prize in Physiology or Medicine, awarded just a year after their successful isolation of insulin.
But we are getting ahead of ourselves.
To cut a long story short, two dogs were sacrificed at the altar of science; one was surgically made diabetic by removing its pancreas, the other’s pancreas was removed and processed to purify its insulin, which was then injected into the former. Dog 1’s dramatically high blood glucose levels came down - success!
Enter James Collip, a biochemist recruited to produce insulin on a larger scale; he used high-strength ethanol to concentrate insulin stored in oxen and pig pancreases until it was pure enough to be tried and tested on a human being. On January 11, 1922, 14-year-old Leonard Thomas lay dying of diabetic ketoacidosis, a then-fatal complication of the disease. Collip’s crude brown distillation of insulin was administered, while Banting waited in the corridor outside; he wasn’t an experienced physician. The first dose had almost no effect, but subsequent injections were miraculous: the boy’s sugar levels crashed, and 'the boy became brighter, more active, looked better and said he felt stronger.'
By the end of the following year, insulin was being produced in commercial quantities, but there were problems with its clinical efficacy. In a healthy person, the pancreas continuously secretes a low, basal level of insulin, which spikes during mealtimes to control the sudden upswing of blood sugar. Artificial insulin would have to be administered too many times a day to achieve base levels. Also, it didn’t act immediately after being injected; patients would have to delay their meals by half an hour or so before it swung into action. Over the following decades, researchers developed variants that would last longer in the bloodstream or dissipate quickly, enabling the limited-dose regimen we follow today.
Insulin and India
In 1923, the Indian Medical Gazette reported: ‘It is ridiculous to suppose that any drug will cure diabetes; if there were any such drug, it would be worth crores of rupees to the person who had the good fortune to know of it’. Unfortunately, the second statement came true.
The average monthly income of each Indian is around 13,000 rupees; the average monthly expenditure of a diabetic patient on insulin alone is 3,000-8,000 rupees. Often not covered by insurance, this recurring expense is paid out of one’s pocket, draining the resources of already impoverished families, and tipping them across the poverty line.
Why is it so expensive? Today, insulin is produced using genetically modified bacteria. Unlike other drugs that are chemically synthesised, insulin is the product of a costly biological process and hence doesn’t have cheap, generic alternatives. Most insulin analogues prescribed in India are imported (and then marked up over 40%), further driving up prices, although the WHO asserts that they have no definitive therapeutic advantage over regular insulin. Possibly incentivised by pharma companies, doctors continue to prescribe the imported analogues; only 1 in 4 insulin vials is made in India. In just one year, their price has shot up by 20%.
So imagine diabetic patients’ jubilation when Indian pharma major Biocon announced that it will supply insulin to low- and middle-income countries at a drastically reduced price, down from around 350 rupees per patient per day, to just seven bucks. Bring out the sweets, in celebration and moderation!
When Banting and his associates announced their results, they could have capitalised on their success and made millions, if not billions, from insulin. Instead, they signed over their patent rights to the University of Toronto - for just $1 each. The discoverers of insulin intended for it to save as many lives as possible; finally, the world has a humane pharma company that will follow their lead.