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The Chemist Who Made Insulin Usable: James Collip and the Purification of a Peptide
Frederick Banting and Charles Best are the names most people know. The person who made insulin safe to inject is much less famous. James Bertram Collip was a biochemist on sabbatical from the University of Alberta, and in the winter of 1921 he was asked to help with a problem: the extract worked in dogs, but it was too crude for people.
Key takeaways
- Banting and Best’s extract contained insulin but also many other pancreatic substances.
- Collip developed a method that used alcohol to remove impurities step by step.
- A rabbit test, based on how far the extract lowered blood sugar, gave a way to measure potency.
- His purified extract was the one that worked for Leonard Thompson on January 23, 1922.
- Later, he also isolated a parathyroid hormone preparation, another peptide.
The problem with the first extract
Banting and Best could keep diabetic dogs alive with an extract of pancreas. It was a major achievement, but the liquid was a thick mix of many biological molecules. Injected into a person, it could cause fever, pain and abscesses, as Leonard Thompson’s first dose showed. It was also inconsistent: two batches could differ greatly in strength. A medicine needed to be cleaner and measurable.
Alcohol as a tool
Collip approached the problem like a chemist. Many biological molecules behave differently in alcohol, which is a gentler solvent than water for some substances. By adjusting the alcohol concentration, he could make unwanted material come out of solution while keeping the active hormone dissolved, and then recover the hormone in a second step. Reports describe him finding a concentration that gave a cleaner product, then refining the process until it could be repeated.
This is the same logic behind modern purification: separate molecules by some property, step by step, and check the result at each stage. Today the tools are chromatography and mass spectrometry, described in our testing guide, rather than alcohol precipitation.
Measuring potency with rabbits
Cleaner extract was not enough. People needed to know how strong each batch was. Collip used rabbits, which respond to too much insulin with a drop in blood sugar severe enough to cause convulsions. Comparing batches by their effect in fasting rabbits gave an early way to define a unit of activity. That is the origin of the idea that insulin dosing is measured in units.
Measuring a biological effect is not the same as measuring identity or purity, which is why modern labs use both kinds of tests. Our dose-response guide and amino acid analysis post show how each works.
From laboratory to pharmacy
With the new extract in hand, the Toronto group treated Leonard Thompson, and then other patients. Demand was immediate and enormous. The University of Toronto soon worked with the pharmaceutical company Eli Lilly, which developed large-scale production in 1923. Banting, Best and Collip each sold their patent rights to the university for a symbolic one dollar, so that insulin would be widely available.
Another peptide, a few years later
Collip went on to a long career in endocrinology. In the mid-1920s he prepared an extract of the parathyroid gland that raised calcium levels in animals, work that led to the discovery of parathyroid hormone, a larger peptide hormone. His methods and his habit of measuring potency carefully shaped the whole field.
What it means for peptide quality today
- A peptide has to be separated from everything else made along with it.
- Strength and purity need independent measurement.
- Reproducibility between lots is part of quality, as in batch-to-batch variability.
- A report is only useful if it can be tied to the product in your hands, as in our lab report checklist.
The bottom line
Collip’s purification showed that a peptide in a vial is only as good as the work that separated it from its impurities. It remains the foundation of every purity claim made today. To see what that documentation looks like for our products, visit the lab reports page.
Related reading
- Leonard Thompson, the first insulin patient
- HPLC versus mass spectrometry
- Batch-to-batch variability
- Browse the full Research Library
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For laboratory research use only. Not for human or veterinary use, and not intended to diagnose, treat, cure or prevent any condition. This article is educational and is not medical advice.