In the late 1940's and early 1950's, Sanger demonstrated that the insulin molecule comprised two chains, A and B, linked by disulfide bridges. Two possibilities for the evolution of this kind of structure suggested themselves. The first was that the two chains were made separately in the beta cell and then united to form the final product. Subsequent investigations lent indirect support to this hypothesis. Isolated separately from crystalline insulin, the A and B chains—neither having biologic activity by itself—were made to reunite, with resulting return of activity.1 Similarly, the joining of separate A and B chains in the in vitro synthesis of insulin also resulted in a compound with measurable hypoglycemic properties which neither chain alone possessed.2 Perhaps, then, this was the way the beta cell made insulin.
The second possibility, not necessarily excluding the first, was that the insulin molecule was a derivative of a larger