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The Dog Experiment That Found Calcitonin, and Why Salmon Made the Best Version
In 1961, a Canadian physiologist named Harold Copp was studying how the body keeps blood calcium steady. He found something that did not fit the textbook, and a new peptide hormone came out of the surprise. Its most useful form, years later, came not from humans or mammals but from salmon.
Key takeaways
- D. Harold Copp, at the University of British Columbia, perfused the thyroid and parathyroid glands of dogs with high-calcium blood.
- Calcium fell faster than removing parathyroid hormone could explain.
- He proposed a second hormone that lowers calcium and named it calcitonin.
- It was later traced to the C cells of the thyroid, and found to be a peptide of 32 amino acids.
- Salmon calcitonin is much more potent than the human form and became the version most studied.
The textbook story
By 1960, scientists knew that parathyroid hormone raises blood calcium. If calcium is too low, the glands release more hormone, and if calcium is high, they release less. That was a neat feedback loop, and it had no obvious need for a second hormone.
A result that did not fit
Copp and his team designed an experiment to test the loop directly. They perfused the glands in anesthetized dogs with blood that was high in calcium and watched the response. Calcium in the animals fell sharply, and it fell faster than simply turning off parathyroid hormone could account for. Copp concluded that the glands must also release a hormone that actively lowers calcium. He named it calcitonin, from a word root meaning to set the calcium level.
Where it really comes from
Copp believed the hormone came from the parathyroid. Other researchers soon found that it was made in the thyroid, in a population of cells called C cells, which have a separate origin in the embryo. The source turned out to be different from what Copp expected, but his core result, a calcium-lowering hormone, stood.
The structure
Calcitonin is a peptide of 32 amino acids. It has a ring at the front closed by a disulfide bond between two cysteines, and the last amino acid is an amidated proline. Both features matter for activity, as explained in our cysteine post and our terminal modifications post.
Why salmon
Calcitonin from several species was compared, and the version from salmon proved far more potent than the human form in assays. Fish calcitonin is made in a gland called the ultimobranchial body, and nature seems to have tuned it to bind the receptor well. Because it is both more potent and more stable, salmon calcitonin became the standard form for study and has been used in nasal and injectable preparations. It is a nice example of how comparing sequences between species can lead to a better molecule, as in the amylin story.
Lab lessons
- A result that does not fit the model can be the start of a discovery.
- A peptide hormone can arise from a different tissue than first thought.
- Species comparison is a design tool.
- Receptor assays such as cAMP functional assays are used to compare potency across versions.
The bottom line
Calcitonin began with a dog experiment that disagreed with the textbook. The practical lesson is to measure carefully and follow the data. Browse more peptide history in the Research Library and our history of peptide drugs.
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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.