While developing his rabbit assays, for the activity of insulin, Collip made an interesting observation: too much insulin could be deadly. He found that more insulin would reduce the rabbit’s blood sugar to dangerous levels. If blood sugar fell below a critical level, the rabbit would go into convulsions and die. This was called “hypoglycemia,” or too little sugar. It is a problem that plagues people with diabetes even today.
Although deadly, hypoglycemia in humans is easily rectified. You simply consume more sugar or simple carbohydrates. The challenge is to recognize the mild symptoms, which can vary in different people, but might include dizziness, sweating, drowsiness and a pounding heartbeat. Severe symptoms can include impaired vision, confusion, seizures, and unconsciousness. The severe symptoms alter the person’s mental state, sometimes preventing them from consuming more sugar.
Standardization of insulin doses was important for preventing accidental insulin overdoses, which lead to hypoglycemia. Today, insulin is measured in “international units” (IU). 1 IU is defined as 34.7 micrograms of pure crystalline insulin. However, in the 1920’s people had no way to measure the mass of pure insulin. Instead, a unit was defined based on its observed activity.
Collip first defined a unit of insulin with his rabbit assays. Initially, he injected insulin into a rabbit and measured how much its blood glucose levels dropped. This required two measurements of its blood sugar, a process which was neither quick nor extremely accurate. Collip noted the hypoglycemic reaction in rabbits: convulsions, then coma, then death. To speed up his work, he defined one unit of insulin to be the amount of insulin that induced the hypoglycemic reaction in the rabbit.
Macleod, as the overall director of research, was concerned with the budget and expenditures. Rabbits cost $1.25 each and Collip was killing many rabbits with his assays. Macleod suggested that the rabbits could be saved, or resuscitated, with glucose. This simple step saved many rabbits and money.