What Were Those Crystals? The Dissolution and Disintegration of Insulin-Reply

In Reply. —We are pleased that Drs Massey and Anderson have confirmed our observation that cuboidal crystals are present in commercial preparations of NPH insulin. We concur with their observation that these crystals are unlikely to be classic four-zinc ultralente insulin crystals. Unfortunately, they do not state specifically what they believe the composition of these cuboidal crystals to be. The previous studies cited by Drs Massey and Anderson define the optimal conditions under which ultralente insulin crystals form. However, these studies do not prove that an ultralente type of crystal cannot be produced over an extended period of time at a slow rate. The crystallization of insulin is a complex process that is dependent on the environmental conditions and the crystallization media. Different forms of insulin may coexist in the same media, as is evidenced by Lente Insulin, which is composed of both amorphous and rhombohedral crystals.1 It is