What Macleod Brought to the Discovery of Insulin
How Many People Does It Take To Turn a Hormone Into a Treatment?
In January 1922, a teenager named Leonard Thompson received an experimental pancreatic extract at Toronto General Hospital. The first attempt was disappointing. A second preparation later that month produced a marked improvement. Between those two injections lies much of the answer to who discovered insulin. An idea about the pancreas, an experiment in a dog and a preparation safe and effective enough to give a sick child were distinct achievements.
In 1923 the Nobel Prize in Physiology or Medicine went to Frederick Banting and John James Rickard Macleod. Banting shared his prize money with Charles Best. Macleod shared his with James Collip. Four names remain central to the story because four people helped solve different parts of the problem. The Nobel roll lists two because an award is a decision made at a particular moment, under particular rules, on the evidence and nominations before a committee.
What Did Scientists Know Before Banting Began?
Doctors had recognised diabetes long before they understood insulin. In the form now called type 1 diabetes, the body produces little or no insulin. Glucose accumulates in the blood while the body struggles to regulate how fuel is used and stored. Before insulin therapy, severely restricting food could sometimes prolong life. A child might survive longer on a diet that left painfully little strength for living.
Experiments in the nineteenth century had connected removal of the pancreas in animals with diabetes. Researchers suspected that specialised tissue within the organ produced an internal secretion important for glucose regulation. The difficulty was getting a useful preparation out. The pancreas also produces digestive enzymes. Grinding up the whole organ produced material containing many things besides the substance researchers wanted.
Several investigators before Toronto obtained evidence that pancreatic extracts could affect diabetes in animals. These contributions are one reason national claims to have discovered insulin can become so contentious. Asking who first saw an effect in a laboratory yields a different history from asking who produced a reliably useful human treatment. Recognition for Toronto need not make the preliminary observations elsewhere disappear.
What Was Banting’s Idea?
Frederick Banting was a Canadian surgeon. In 1920 he proposed tying off the pancreatic ducts in animals, waiting for much of the tissue associated with digestive secretions to degenerate, then extracting material from what remained. He hoped the tissue responsible for the internal secretion would survive in a form from which it might be recovered.
It was a productive experimental proposal even though it did not become the essential manufacturing method. In retrospect it is tempting to tell the story as though Banting wrote down a recipe, followed it and obtained modern insulin. The value of the idea was that it gave a team a concrete experiment worth trying. Subsequent work could show which parts of the proposed procedure were actually necessary.
Banting approached Macleod at the University of Toronto. Macleod was an established specialist in carbohydrate metabolism. He had the laboratory facilities, animals, methods and scientific experience a young surgeon working alone lacked. Granting space for an experiment can sound like an administrative footnote until one asks what would count as a convincing result and who had the expertise to answer.
What Did Charles Best Contribute?
Best worked alongside Banting during the summer of 1921. Success depended on animal care, surgical work, making extracts and measuring changes in blood sugar. A striking fall in one reading might reflect a genuine biological effect, a measurement problem or a change in the condition of a sick animal. Repetition and careful comparison helped turn an exciting possibility into a result other researchers could examine.
The two men became closely associated in public memory. Their partnership also provided an attractive narrative for newspapers: a young surgeon and student, working with limited resources, find something that had escaped senior scientists. There is truth in the energy and persistence that picture captures. The more it hardens into a complete explanation, however, the harder it becomes to see the additional work between an animal experiment and Leonard Thompson’s hospital bed.
A dog responding to an extract supplied evidence that an active substance was present. It could not tell a clinician which contaminants were present, whether successive batches had comparable strength or how a human patient would respond. Those questions assumed greater importance precisely because Banting and Best had found something promising.
Why Was James Collip’s Work So Important?
Collip was a biochemist. His task involved purifying the extract so that the active material could be separated from substances that made earlier preparations unsuitable. Manipulating alcohol concentrations helped him separate components of the pancreatic mixture. The craft lay in finding conditions that retained biological activity while removing unwanted material. An extract can look cleaner while losing the substance the patient needs.
In a modern hospital, a dose written on a chart presumes a preparation with known strength. In Toronto, the researchers first had to develop ways of comparing biological activity between batches. Even if two containers held the same volume of fluid, they did not necessarily contain the same amount of active substance. Purification and measurement were central to the discovery’s medical meaning.
Thompson’s first injection on 11 January did not produce the result the team needed and caused a local reaction. A more purified preparation was used on 23 January. The response provided much stronger clinical evidence. Telling only the story of the first injection celebrates a date while missing the experimental correction that made January 1922 a turning point.
What Did Macleod Do Beyond Lending the Laboratory?
Macleod’s knowledge of metabolic research helped shape interpretation, testing and the team’s expansion. He brought resources and collaborators to a problem that had outgrown its initial arrangement. He also helped present the work to the wider scientific community. Scientists elsewhere needed to know how the experiments had been conducted, which measurements had changed and whether the effect could be reproduced.
The division of labour became a source of personal conflict. Banting believed Best deserved recognition and resented the prominence given to Macleod. Accounts written by people close to the dispute reflect different loyalties. A person who spent a summer performing experiments and a person responsible for the scientific programme could each reasonably think the other’s account had left something out.
There is a larger question here about the language of discovery. An experimental result occurs at a bench. A finding becomes convincing through criticism, replication and the elimination of alternative explanations. A treatment becomes possible through chemistry, clinical work and manufacturing. Awards generally require a small number of names and a short citation. Medical history rarely cooperates.
Why Did the Nobel Committee Choose Only Two?
The 1923 award named Banting and Macleod for the discovery of insulin. The contemporary nomination process is important. Best was not nominated for that prize year. An answer that says the committee simply examined four equal candidates and crossed off two already misdescribes the process. Nor does the later division of prize money turn Best and Collip into Nobel laureates. It records what the recipients chose to do with their shares.
Banting’s gesture towards Best and Macleod’s towards Collip are often narrated as a neat correction of an injustice. They also preserve the outlines of the original disagreement. Banting emphasised the work of his close experimental partner. Macleod recognised the biochemist whose purification had helped make effective human treatment possible. Each gesture illuminates a different part of the achievement.
Modern readers have access to a longer record of what happened next. They know that insulin transformed clinical practice, that large-scale production mattered and that the conflicts over credit endured. The committee in 1923 was rewarding work of remarkable immediacy. Historical judgement does not have to duplicate its selection to understand why the award was made.
What Changed Once Insulin Left Toronto?
More patients needed treatment than a university laboratory could supply. Scaling up required access to animal pancreases, manufacturing methods, quality control and distribution. The difference between having a vial for one patient and guaranteeing a supply for thousands is a difference in medicine, as well as in industrial capacity. A treatment taken repeatedly has to be available repeatedly.
The Toronto researchers’ patent arrangements are frequently invoked in arguments about the price of insulin. The early patents were assigned to the University of Toronto for nominal sums. That history helps explain why access was bound up with the discovery from the beginning. It cannot by itself explain the prices of different modern formulations in different health systems. A century of changes in production, patents, regulation and purchasing stands between the original extract and the insulin people use today.
The improvement in patients could be extraordinary, but insulin was a treatment. People still needed a continuing supply, food, monitoring and adjustments to the amount taken. An account ending at the first successful injection leaves the patient behind at precisely the moment the rest of their life begins.
What Did the First Human Result Actually Prove?
An individual patient responding to an experimental preparation was an immensely important observation. It could show that a result achieved in animals might translate into clinical benefit. It could also reveal reactions that animal experiments had given researchers little reason to anticipate. It could not establish the correct long-term regimen for everyone with diabetes. Those questions required experience with more patients, more consistent preparations and continued observation.
The wording of the historical claim therefore matters. Calling Thompson the first patient to receive the Toronto preparation gives the first January injection its proper place. Calling that first injection an unqualified success deprives Collip’s subsequent work and Thompson’s second treatment of much of their significance. The two dates are most illuminating when they are allowed to remain two dates.
It is also worth noticing the different timescales within a single treatment. A researcher might measure a biochemical change within hours. A family wanted to know whether a child could eat, grow, go home and have a future. A hospital needed to know whether an effective dose could be repeated tomorrow. One discovery had to answer all three expectations before it could transform routine care.
Why Is the Pancreas Such a Difficult Place to Find a Medicine?
The organ does several jobs in a remarkably small space. Much of its tissue produces digestive substances that travel through ducts towards the gut. Small groups of endocrine cells release hormones into the circulation. Removing the whole pancreas takes away both functions at once. Observing diabetes after removal tells an experimenter that something crucial has been lost, but does not hand them a clean sample of it.
The extraction problem can be understood without a chemistry degree. Imagine finding that a library contains a document you need, while the procedure for opening the building sets off sprinklers that can destroy the paper. The desired material is present. The way you seek it may change or destroy it. Researchers had to test whether a failure meant that their hypothesis was wrong, the substance had been damaged or the accompanying material had obscured its effect.
This also explains how a scientifically imperfect starting idea can lead to a decisive discovery. The value of an experiment is partly in what its results allow researchers to try next. Once the Toronto team could repeatedly observe an effect, it had a test for assessing different preparations. A biochemical fraction could be followed by its activity even before the team possessed the detailed molecular description later generations would take for granted.
Finally, look at the discovery from the position of a patient waiting outside Toronto. News could cross an ocean much faster than a reliable supply of extract. A headline announcing a breakthrough might arrive while a local doctor still had none to give. That gap between knowledge and access remains part of the history of insulin, and helps explain why families and clinicians have often told the story differently from prize committees.
Why Is World Diabetes Day on Banting’s Birthday?
World Diabetes Day falls on 14 November, Banting’s birthday. A calendar needs a single date. History can accommodate more than one person. Remember Banting by the experiment he proposed, Best by the work of testing extracts, Collip by purification and Macleod by the research programme that helped carry the result into medicine.
Then return to Thompson. Between his first and second injections, the question changed from whether an extract could be administered to whether it could help a child in a clinically meaningful way. His experience supplies a standard for judging every claim about discovery. Finding a substance was extraordinary. Bringing the right preparation to the bedside was the achievement on which a life depended.
