Insulin: The 14-Year-Old Who Changed Diabetes Treatment

In January 1922, a 14-year-old boy at Toronto General Hospital was getting worse despite a diet of about 450 calories a day. He had diabetes, had lost weight and spent much of his time in bed. His body was passing large amounts of sugar into his urine.

His name was Leonard Thompson. The doctors' published case report called him L.T.

On January 11, he received an extract made from pancreas tissue. His blood sugar fell by about 25%, but the team reported no clinical benefit. The first attempt had changed a measurement without producing the recovery they needed.

Twelve days later, treatment with a better preparation began. The report describes a boy who became more active, looked better and said he felt stronger. Insulin had begun to change what treatment could do for severe diabetes.

Thompson entered the hospital on December 2, 1921. He weighed 65 pounds. The examination recorded poor nourishment, hair loss and an acetone smell on his breath. He was passing several liters of urine a day.

Doctors adjusted his food over the following month. By January 4, his daily intake totaled approximately 450 calories. The report says that no further change in diet was made during the period it describes. Even under that strict restriction, his condition deteriorated.

To understand why, start with insulin's normal job. Insulin is a peptide hormone, built from chains of amino acids. These are the small units that make up proteins. It helps glucose move from the blood into cells for use as energy. In type 1 diabetes, the immune system destroys the pancreatic beta cells that produce it. As insulin becomes scarce, glucose builds up in the blood.

The body can also break down fat rapidly, producing substances called ketones. When these accumulate excessively, they can make the blood dangerously acidic. The acetone smell and positive urine tests in Thompson's record were signs of this disrupted metabolism.

Reducing food intake could limit the glucose arriving from meals. It could not replace the missing hormone. For a growing child who was already severely underweight, the remaining room to cut food was painfully small.

That was the problem the Toronto team faced. Their patient needed a way to use energy while bringing the excessive sugar and ketone levels under control. A medicine that could supply the pancreas's missing activity offered a route to do that.

Frederick Banting and Charles Best had been testing pancreatic extracts in animals at the University of Toronto. Their work built on earlier experiments connecting the pancreas to diabetes. Removing the organ from dogs caused severe disease; extracts from it sometimes lowered blood sugar.

Turning that observation into treatment required a preparation that retained useful activity through extraction and could be given to a patient. A pancreas contains many substances, including digestive enzymes. Processing the whole organ did not automatically produce a usable medicine.

Banting and Best initially worked with glands altered by tying off their ducts. They later tested fetal calf tissue and developed extracts from adult cattle pancreas. In their animal work, these preparations lowered blood sugar and reduced the sugar lost in urine.

Biochemist James Collip then worked on isolating and purifying the active material. His contribution helped produce an extract suitable for human testing. Physicians Walter Campbell and Andrew Fletcher observed the patients at Toronto General Hospital.

The original report carries all five names. Reading it makes the work visible as a series of linked problems: obtaining active material, preparing it for administration, and measuring its effect in a sick person. Each step affected whether the next one could succeed.

The first administration on January 11 used a less concentrated extract than the later treatments. Although blood sugar fell, the report says Thompson received no clinical benefit. That distinction is worth retaining when the story gets shortened to the first insulin injection.

Beginning January 23, the team gave the improved extract through February 4, with interruptions on January 25 and 26. The daily record shows a steep decline in urinary sugar after treatment began. Ketones disappeared from the urine, and the doctors observed the improvement in Thompson's activity and appearance.

On January 22, he passed 148.5 grams of glucose in 24 hours. On January 24, the recorded amount was 8.7 grams. These figures measure sugar lost in urine. They are different from a blood-glucose reading taken at one moment.

The report includes a table of daily measurements, which lets us follow what happened between the first improvement and the end of treatment. When treatment paused on January 25 and 26, urinary glucose rose. It fell again after administration resumed. The amounts still varied from day to day, and the extract quantities varied too.

This was an early clinical observation in a very ill patient. There was no randomized control group. His diet was held constant during the treatment period, which helped the team interpret the change, but the record was still a case report with the limitations of early preparations and tests.

Thompson's own report of feeling stronger added something the sugar measurements could not supply. A lower laboratory value became meaningful alongside a change in how the boy felt and moved through the ward.

From February 5 through February 15, Thompson received no extract. Sugar returned to his urine in large amounts, and traces of acetone reappeared. After treatment resumed, the team again recorded lower sugar excretion and the disappearance of acetone.

The improvement depended on continued treatment. The extract supplied biological activity his body needed, while the underlying disease remained. The interruption made that dependence visible within the same short patient record.

By February 22, the researchers had observed seven people treated with the preparations. They reported clinical improvement in all seven and described another patient whose severe fatigue improved after treatment. They were beginning to see the initial result recur beyond Thompson.

The report also recognized that careful control was necessary. Preparations had to be purified further, and their effects had to be managed. A discovery that could alter metabolism so strongly brought a practical obligation to deliver a reliable amount of active medicine.

For Thompson, that meant ongoing access. The University of Toronto's archive records that he lived for another thirteen years on insulin. His story continued well beyond the January dates usually attached to the discovery.

The first extracts came from animal organs. As the number of patients grew, production had to expand while keeping the medicine consistent. Toronto collaborated with Eli Lilly in 1922 to increase supply and extend the clinical work.

Insulin's activity had to survive each stage between the source tissue and the patient. A preparation that varied from batch to batch made treatment harder to control. Manufacturing quality therefore belonged inside the medical problem from the beginning.

Decades later, recombinant DNA technology changed the source of insulin. Scientists could give microorganisms genetic instructions for making human insulin components. Cells supplied the protein-making machinery, and further processing produced the medicine.

In 1978, researchers at City of Hope and Genentech developed a method for biosynthetic human insulin. The FDA approved Humulin on October 28, 1982. It was the first approved medical product made using recombinant DNA technology.

Human insulin supplies a concrete example of how a manufactured medicine can reproduce a hormone found in the human body. The production process and the resulting molecular identity are separate facts worth understanding.

The practical questions then concern the specific product, its testing and its use. Insulin's history provides its own evidence. Every other peptide still needs evidence that fits the benefit being claimed for it.

Once people could live with insulin treatment, researchers could examine how glucose control affected their health over time. The Diabetes Control and Complications Trial enrolled 1,441 people with type 1 diabetes and followed them for an average of 6.5 years.

Intensive treatment used an insulin pump or at least three daily injections, with frequent glucose checks. The comparison group received conventional treatment of that period. Both groups used insulin.

Among participants without diabetic eye disease at the start, intensive treatment reduced its development by 76% relative to conventional treatment. Among those who already had mild eye disease, it reduced progression by 54%. These were different starting groups and different outcomes.

Intensive treatment also increased the risk of hypoglycemia, or dangerously low blood glucose. The NIDDK's account of the trial makes that tradeoff explicit. Glucose management has to protect against excessive lows while reducing long-term exposure to high glucose. Individual treatment decisions need that full picture.

The trial extended the question raised in Thompson's ward. Researchers could now measure whether a treatment strategy helped preserve health across years of living with diabetes.

The next time a peptide study catches your attention, look for the outcome that matters to the person receiving it. Thompson's report includes both chemical measurements and a change in his daily function. The later trial follows the risk of tissue damage over years.

Then check how long the observation lasted and what happened in the comparison group. A treatment effect over a few hours answers a different question from protection over several years. The original insulin record also shows why treatment interruptions and preparation quality deserve attention.

Those details make the evidence useful. They explain why the same familiar word, insulin, can carry a story about rescuing a sick child, producing a reliable medicine and protecting health over a lifetime of treatment.

Thompson's doctors recorded him becoming more active and feeling stronger. Keeping that improvement possible required insulin to remain available after the first successful injection.

Which familiar medicine's original study would you like to understand next? Reply and tell me.

1. Banting FG and colleagues. Pancreatic Extracts in the Treatment of Diabetes Mellitus. CMAJ, 1922. 2. University of Toronto, Thomas Fisher Rare Book Library. Leonard Thompson archival exhibit. 3. FDA History Office. 100 Years of Insulin. 4. NIDDK. Type 1 Diabetes. 5. Aiello LP for the DCCT/EDIC Research Group. Diabetic Retinopathy and Other Ocular Findings. Diabetes Care, 2014. 6. NIDDK. Blood Glucose Control Studies for Type 1 Diabetes: DCCT and EDIC.

For entertainment and education only. Not medical advice. Talk to your doctor before starting anything.