Our current conclusion provides a resolution for several issues regarding chronic hypoxia: the reason why cancer cells lacking VHL are not capable of degrading HIF-1α during prolonged periods of hypoxia and why cancer cells show less agression under conditions of chronic hypoxia- compared with those of acute-hypoxia, and the mode of action of metabolites in chronic degradation of HIF-1α. The gene discussed is VHL; the disease is cancer.