2000 Global Researcher Conference Proceeding
March 10 - 12, 2000
| Conference: | 2000 Global Researcher Conference |
|---|---|
| Title: | The last fifty years; a retrospective on NDI |
| Author: | Crawford, M.D., John D. |
| Institution: | Harvard Medical School |
The second half of the 20th century has been an exciting period in all of science. Those of us with a particular interest in nephrogenic diabetes insipidus have seen the disorder taken from folklore through definition of its pathophysiology, endocrinology, and Mendelian genetics to our present era of molecular understanding. Forssman in Europe and Waring, Kadji and Tappan in this country provided definition in the nineteen forties. The fifties saw an elucidation of membrane physiology, active transport, countercurrent concentration and the synthesis of vasopressin. The sixties brought the thiazides with their paradoxical ability to ameliorate NDI but also DDAVP, the remarkable result of Zaroal's tinkering with the AVP molecule. This not only revolutionized treatment of central diabetes insipidus but provided general insights to receptor diversity. The late sixties saw the launching of the Hopewell hypothesis. The nineteen seventies was the decade in which Robertson and his collaborators succeeded in radioimmunoassay of AVP in physiologically important concentrations. The eighties were years of ferment presaging the knowledge explosion of the nineties. The need for a mechanism to understand NDI beyond the alteration in the V2 receptor emerged. The basis for the additive effect of the prostaglandin inhibitors to that of the thiazides in X-linked NDI began to be glimpsed. The nineteen nineties saw a flowering of molecular genetics in all fields. In our area, this cast light on both central and peripheral diabetes insipidus. Defects in the central secretion and processing of AVP have been elucidated. The concept of a single defect in the peripheral V2 AVP receptor predicted in the Hopewell hypothesis was torpedoed; now more than 80 discrete genetic errors have been characterized. The role of the aquaporins in water conservation has provided insights to the rarer types of NDI that are not X-linked as well as to some medically important circumstances of excess water retention.
Given the ever accelerating pace of knowledge during the last half century, can anyone predict the excitement of the next fifty years?