The Son of the Manse Who Helped Conquer Diabetes

A Son of the Manse

John James Rickard Macleod (J.J.R. Macleod) was born on 6 September 1876 in the Free Church manse at Clunie, near Dunkeld in Perthshire, the first child of the Reverend Robert Macleod and his wife Jane Guthrie McWalter. "Jack", as he was known, moved north as a small boy when his father was called to Keith in Banffshire, and in late 1883 the family settled in Aberdeen, where Robert Macleod served as minister of the John Knox Free Church on Gerrard Street for over thirty years.

It was in the Granite City that Macleod's intellect took shape. He attended Aberdeen Grammar School, then entered Marischal College at the University of Aberdeen to study medicine, graduating with honours (M.B., Ch.B.) in 1898 and winning the Anderson Travelling Fellowship, which carried him to the Institute of Physiology at the University of Leipzig for a year of postgraduate study in physiological chemistry.

At Aberdeen he had been shaped by Professor John James MacWilliam, whose emphasis on critical thinking and experimental rigour set the pattern for Macleod's career. Historians have traced Macleod's "deep conservatism as a scientist" — his insistence on controls, repetition and proof — directly to this Scottish education. In Toronto, twenty years later, that inheritance would prove decisive, and would also make him an enemy.

The Making of an Authority

From Leipzig, Macleod moved to London in 1899 as Demonstrator in Physiology at the London Hospital Medical School, becoming Lecturer in Biochemistry in 1902 and earning a Diploma in Public Health from Cambridge. His reputation as a lucid lecturer and prolific researcher crossed the Atlantic, and in 1903, aged just 27, he was appointed Professor of Physiology at Western Reserve University in Cleveland, Ohio. That same year he married Mary Watson McWalter and sailed for North America.

In Cleveland, Macleod turned to the subject that would define him: carbohydrate metabolism. His series of papers under the heading "Studies in Experimental Glycosuria" appeared in the Journal of Physiology, and formed the basis of his 1913 monograph Diabetes: Its Pathological Physiology. By 1918, when he accepted the Chair of Physiology at the University of Toronto, he had published six books and dozens of articles, sat on the editorial boards of leading journals, and was regarded as one of the foremost authorities on diabetes and sugar metabolism in the English-speaking world.

One detail matters enormously for what followed. Macleod's own theory of diabetes still emphasised the liver and nervous system, and he remained sceptical of the idea of an "internal secretion" of the pancreas. When a young surgeon arrived with exactly such an idea, Macleod was not an easy mark but a hard-headed expert who demanded proof.

"I Scarcely Know Where to Begin": Banting Meets Macleod

In late 1920, Frederick Grant Banting was a struggling young surgeon in London, Ontario, with no research experience, no publications and not yet even a doctorate. After reading an article on the pancreas, he scribbled a late-night note: "Ligate pancreatic ducts of dog. Keep dogs alive till acini degenerate leaving islets. Try to isolate the internal secretion of these to relieve glycosuria." The idea was that tying off the pancreatic ducts would destroy the cells producing digestive enzymes — which Banting believed were destroying the elusive anti-diabetic secretion before it could be isolated — leaving the islets of Langerhans intact.

Banting brought the idea to Macleod in November 1920. Macleod was, by most accounts, unimpressed; the hypothesis was neither especially original nor, as it turned out, physiologically sound. But he recognised that even a negative result could be useful, and he had a mandate to build Toronto's research capacity.

What Macleod then supplied was not a room. It was laboratory space in a properly funded department, a supply of experimental dogs, the equipment, instruction in the necessary surgery — Macleod personally taught the surgeon Banting how to perform a canine pancreatectomy — and the services of a student assistant. Two recent honours graduates, Charles Best and Clark Noble, were to share the summer's work; they tossed a coin, and Best won the first turn. He never gave it up.

The Summer of 1921 — and the Absent Professor

Banting and Best performed their first operation on 17 May 1921. Macleod worked alongside them for roughly a month before leaving in mid-June for his planned summer in Scotland, partly to represent Toronto at a conference of Empire universities at Oxford. This holiday is the hinge on which the entire controversy turns — and it needs stating precisely. Macleod was absent for part of the summer's dog experiments. He was not absent from the discovery of insulin, which took another eighteen months and a great deal more than those experiments.

Through the sweltering Toronto summer, amid heavy losses of dogs and many setbacks, Banting and Best injected extracts from duct-ligated dog pancreas into diabetic dogs and saw blood sugar fall. Excited, they wrote to Macleod in Scotland: "I have so much to tell you," Banting's letter began, "that I scarcely know where to begin."

When Macleod returned in September, he did what any rigorous scientist would: he pointed out that the results were inconsistent and lacked proper controls, and urged them to repeat and refine the work. To Banting — raw, insecure and broke — this was not scientific caution but theft. He stormed out, reportedly raging, "I'll show that little son of a bitch that he is not the University of Toronto."

It is worth being exact about what the summer achieved. As the historian Michael Bliss concluded, Banting and Best's crude, impure extract barely matched what Georg Zülzer had achieved in Berlin some fifteen years earlier, and their duct-ligation method was soon abandoned in favour of extracts from fresh whole beef and pork pancreas. The "great idea" had been useful chiefly to start the work. The discovery still had to be made.

Collip and the Breakthrough

Recognising that turning a promising extract into a safe, reliable medicine required chemical expertise neither he nor Banting and Best possessed, Macleod brought in James Bertram Collip, a biochemist from the University of Alberta on sabbatical in Toronto, in December 1921. It was Collip who, working at a feverish pace, found a way to purify the extract — gradually increasing the alcohol concentration of the solution to precipitate out the active principle and leave the toxic contaminants behind.

The stakes became human on 11 January 1922, when Banting and Best's extract was injected into Leonard Thompson at Toronto General Hospital. The result was a disappointment: blood sugar fell only slightly, the ketoacidosis was untouched, and a sterile abscess formed at the injection site.

Then, on 23 January 1922, Thompson received Collip's purified extract. The results were dramatic: his blood glucose fell from 520 mg/dL (28.8 mmol/L) to 120 mg/dL (6.7 mmol/L) — a decline of roughly 75% — and the sugar and ketones vanished from his urine. The boy revived. Leonard Thompson lived another thirteen years on insulin.

The word for the new substance was settled by Macleod, who suggested "insulin" — after the insular tissue, the islets of Langerhans — later acknowledging that earlier researchers had proposed a similar name. And it was Macleod who took the discovery to the world, announcing it on 3 May 1922 to the Association of American Physicians in Washington.

The patient who became the symbol of the miracle was Elizabeth Hughes. She arrived in Toronto in August 1922 weighing 45 pounds and left transformed, her weight climbing to 79 pounds and her diet rising past 2,500 calories a day. She lived to 73, raised a family, and concealed her diabetes for the rest of her life.

The Discovery of Insulin: 1920–1923

1. November 1920

   Banting approaches Macleod in Toronto

   A young London, Ontario surgeon with no research record brings an idea about ligating pancreatic ducts.

2. 17 May 1921

   Banting and Best begin experimental work

   Macleod supplies the laboratory, dogs, equipment and surgical instruction, and works alongside them for roughly a month.

3. Summer 1921

   Pancreatic extracts lower blood glucose in diabetic dogs

   Macleod is in Scotland for a planned summer, partly representing Toronto at a conference of Empire universities at Oxford.

4. September 1921

   Macleod returns and demands stronger controls

   He points out that the results are inconsistent and asks for repetition and refinement. Banting takes it as an attack.

5. December 1921

   James Collip joins the team

   Macleod recruits the Alberta biochemist whose purification work would prove decisive.

6. 11 January 1922

   First human treatment disappoints

   Leonard Thompson, 14, receives Banting and Best's extract at Toronto General Hospital. Blood sugar falls only slightly; a sterile abscess forms.

7. 23 January 1922

   Collip's purified extract transforms Thompson

   Blood glucose falls from 520 mg/dL to 120 mg/dL — roughly 75% — and sugar and ketones almost vanish from his urine.

8. 3 May 1922

   Macleod presents the discovery in Washington

   The announcement to the Association of American Physicians takes insulin to the scientific world.

9. 1923

   Nobel Prize in Physiology or Medicine

   Awarded jointly to Banting and Macleod. Banting shares his money with Best; Macleod shares his with Collip.

Who Actually Discovered Insulin?

Frederick Banting, Charles Best, James Collip and J.J.R. Macleod formed the core Toronto team responsible for turning pancreatic extract into clinically useful insulin. That is the historically responsible answer, and it is now the standard formulation among scholars. Their contributions were different and complementary; there is no single winner to name.

Macleod himself, in his Nobel lecture, described the chain of work in the first person, noting that "under my direction" Banting and Best had shown the extracts reduced hyperglycaemia and glycosuria in depancreatized dogs. Asked by a Toronto Star reporter in November 1923 why he had said nothing of his own share, he replied with a laugh: "Oh, I was only the impresario — the managing director." It was self-deprecating, and also exactly accurate.

Why Was Macleod's Nobel Prize So Controversial?

The 1923 Nobel Prize in Physiology or Medicine was awarded jointly to Banting and Macleod. The decisive nomination came from the Danish laureate August Krogh, who, after visiting Toronto, concluded that while the credit for the idea went undoubtedly to Banting, "he would definitely not have been able to carry out the investigations, which from the start and during all stages, have been supervised by Professor Macleod."

Banting was incandescent. He believed Best, not Macleod, deserved the honour, and initially considered refusing the prize altogether; only the intervention of trusted colleagues persuaded him to accept. He then publicly announced that he would split his half of the prize money with Best, telegraphing him: "Nobel trustees have conferred prize on Macleod and me. You are with me in my share always." Macleod, in turn, announced on 7 November 1923 that he would share his half with Collip, emphasising how difficult the insulin work was to divide and how much it had been a team effort.

The award did lasting damage to Macleod's reputation, because Banting, Best, their allies and to a degree the university promoted what scholars call the "Banting and Best myth": a fairy tale in which two young Canadians made the discovery on their own, with the foreign professor either irrelevant or obstructive. Banting maligned Macleod for the rest of his life, and the two men never spoke again once the bitterness set in.

The injustice cut both ways. Best and Collip, who had genuinely done crucial work, went unrecognised by the committee, and in 1972 the Nobel Foundation officially conceded that omitting Best had been a mistake. Nobel recognition simply did not map cleanly onto a four-person contribution.

How History Reconsidered J.J.R. Macleod

Was Macleod unfairly forgotten? Yes — and the correction came from Canada. In 1982 the Toronto historian Michael Bliss published The Discovery of Insulin, reconstructing the research "day by day, dog by dog" from the original notebooks and documents. Bliss concluded that the discovery was the work of a team of four — Banting, Best, Collip and Macleod — and that history had been "particularly unfair to Macleod".

Bliss noted wryly how the myth had taken hold: "The notion got about that Macleod had not really deserved to share in the prize awarded for the research of those men with such alliterative, assonant and Canadian names, Banting and Best." In the decades since, the more accurate formulation — Banting, Best, Collip and Macleod — has become standard among scholars. Bliss spent more than three decades arguing the case, calling Macleod "Scotland's insulin laureate" in a 2013 lecture and article.

Home to Aberdeen

In 1928, weary of Banting's enmity, troubled by the early signs of the rheumatoid arthritis that would cripple him, and drawn back to his homeland, Macleod resigned from Toronto and returned to Scotland as Regius Professor of Physiology at the University of Aberdeen — succeeding his own former teacher, John Alexander MacWilliam. The return of a Nobel laureate to his old university was celebrated in the local press.

At Aberdeen he revitalised the physiology department, served as Dean of the Faculty of Medicine, sat on the Medical Research Council from 1929 to 1933, and acted as Consultant Physiologist to the Rowett Institute for Animal Nutrition. His students included Hans Kosterlitz, who would go on to pioneer the discovery of endorphins.

Though arthritis increasingly confined him — by 1933 he needed a wheelchair — he kept working, teaching and writing almost to the end, and devoted his spare hours to golf, motorcycling and painting. John James Rickard Macleod died at his home near Aberdeen on 16 March 1935, aged 58, and was buried in Allenvale Cemetery overlooking the River Dee. He and Mary had no children.

Scotland's Claim

For most of the century after his death, Macleod was better remembered in Canada — where even the myth that diminished him at least kept his name in circulation — than in the country of his birth. His Allenvale gravestone modestly omits any mention of the Nobel Prize.

Scotland's belated reckoning came on 12 October 2023, when the world's first monument to him was unveiled in Aberdeen's Duthie Park before a crowd of 300 guests, the ceremonial ribbon cut by the Lord Provost of Aberdeen, Dr David Cameron. The memorial is a life-size bronze by the Ayrshire sculptor John McKenna, depicting "Jack" Macleod seated on a Royal Parks bench with a newspaper at his side carrying a headline referring to his 1923 Nobel Prize. Billed as Scotland's first "storytelling statue", it lets visitors scan a QR code to hear his life story narrated by the Aberdeen-born actor David Rintoul.

The unveiling featured a personal letter from Queen Camilla, who wrote that the statue was "a fitting tribute both to [Macleod's] achievements and to his deep connection to this beautiful city". The campaign was led by John Otto, Founder and Chairman of the JJR Macleod Memorial Statue Society, co-founded with the author Kimberlie Hamilton. "As someone who has been dependent on daily injections of insulin for the past 50 years," Otto told STV News, "it has been a surreal but gratifying experience to watch this long-held dream become a reality."

Why the Discovery of Insulin Changed the World

Before insulin, type 1 diabetes usually meant death within months. After insulin, it became a treatable chronic condition. That is the whole of it, and it is difficult to overstate.

The drug reached the world with extraordinary speed. The University of Toronto sold the patent for one dollar — Banting's principle that "insulin does not belong to me, it belongs to the world" — and Eli Lilly began commercial production in 1923. No Nobel Prize has ever been awarded faster after the breakthrough it honoured: less than two years separated Leonard Thompson's successful injection from the award.

A century on, the scale of the legacy is staggering. According to the International Diabetes Federation's 11th-edition Diabetes Atlas (2025), 589 million adults aged 20–79 — one in nine — now live with diabetes. More than 9.5 million people globally live with type 1 diabetes and depend on insulin to stay alive. Every one of those lives traces back, in part, to a laboratory in Toronto directed by a minister's son from Perthshire.

Myth vs Evidence

The Impresario

Macleod's importance lies not in replacing Banting as the hero of insulin, but in understanding that great scientific discoveries are often collective achievements. Banting initiated the experimental programme, Best worked beside him, Collip made the extract clinically usable, and Macleod supplied the scientific leadership, expertise and institutional framework that turned promising research into one of medicine's greatest breakthroughs. Correcting one myth is not a licence to build another.

A minister's son born in a Perthshire manse, schooled and graduated in Aberdeen, directed the Toronto laboratory that transformed diabetes; came home to Scotland; was largely forgotten by the country of his birth; and, a century later, was finally given a bench in a public park in the city that made him. It is a quieter kind of greatness than the myth allows, and it is the kind that most often makes medicine work.