Some clinicians noted the futileness of standardization. They argued, like Clowes, that only a gross standardization was necessary, since different patients had different reactions to insulin. The cause of this variability in humans would not be understood for some time. The cause, at least part of it, was due to the variability in the immune response in humans. It was the same reason that some people developed the auto immune disease diabetes in the first place. The insertion of foreign proteins (cow/pig insulin) into the human body elicited an immune response. This response could incapacitate some of the injected insulin. The specific response depends on the person, and thus the activity of the insulin depends on the person. Similarly, rabbits probably had differing immune responses to injected cow/pig insulin, contributing to variability in the standard.
The problem of the variability in the standard was finally solved by declaring a large batch of insulin “the standard”. All further insulin preparations could be compared to this standard batch. This would eliminate the individual variability present in the calibration. The challenge was to preserve “the standard” insulin so that it would not degrade over time.
The standard for insulin was prepared at the National Institute for Medical Research in London. It was decreed that one milligram of this standard would correspond to 8 units of insulin. The standard was finalized by 1925. Five different manufacturers of insulin, including Eli Lilly, contributed some insulin. The standardization team combined the insulin, and purified it into a powder form. This powder form of insulin was stable, if kept sealed.
The insulin standard was doled out to laboratories so that they could calibrate their own insulin to a uniform standard. The standard insulin, however, only had a finite amount. A second international standard batch was established in 1935, and a third in the 1950’s. The standards insulin ceased to be useful in the 1970’s. Once the structure of insulin was known, its mass could be calculated, and the quantity of insulin could be measured with a scale.
The current standardization of insulin is known as the International Unit (IU). One International Unit of insulin consists of 0.03846 mg of human insulin, or equivalently 26.0 IU of insulin is 1 mg.