Historical News and Views in 2004

In 1995, Mark Keating and colleagues identified two genes responsible for congenital long QT syndrome, a cause of sudden cardiac death. Perturbations in the ion channels that orchestrate the beating heart were central to the disorder. This revelation provided a molecular model for the study of ventricular arrhythmias and enabled further dissection of the genetic defects underlying subtleties in the cardiac phenotype. Soon, these discoveries will be further translated to clinical medicine, with the expected release of one of the first comprehensive clinical genetic tests in cardiology.

Well over ten years ago, hints begin to emerge that the melanocortin system, implicated in adrenal function and skin pigmentation, might also regulate energy balance. In the 1990s, speculation gave way to hard data: a melanocortin receptor highly expressed in the brain was firmly established as a central regulator of food intake and fat mass.

The first X-ray crystal structures of gp41, the protein that mediates fusion of HIV-1 to target cells, were solved in the mid-1990s. The structures provide a foundation for understanding viral entry and the mechanism of action of compounds that block fusion. The first fusion inhibitor has recently entered the clinic, and the hope is that more potent and broadly active compounds, based on molecular design, will follow.