The evolution of insulin therapy.

Evolution in medicine is generally driven by clinical need, hand in hand with opportunities generated by novel chemical and mechanical engineering technologies. Since 1921 that has been a continuing paradigm for insulin therapy, some advances being a continual process, and others arising from external scientific or engineering developments. Purification of insulin preparations was an early issue, resolved in the 1970s, then challenged by the switch to manufacture in microorganisms. The nature of insulin was established serially, in 1928 as a polypeptide, in 1955 by amino acid sequence, and later by 3-dimensional structure (1969), laying foundations for understandings on routes of administration, and later the engineering of novel insulins. Insulin was the first, and remains the predominant, pharmaceutical therapy to benefit from scientific advances underlying the genetic code, and thus recombinant DNA technology. Advances in mechanical and chemical engineering have contributed to important changes in insulin delivery devices. Biological science, including both cellular mechanisms and whole organism physiology, has led to considerable understandings of clinical defects in insulin action, but currently has been disappointing in its applicability to the insulins available for clinical practice, something perhaps now changing. The pathways of these changes are reviewed here.