The molecular pathology of hemophilia A.

kind. I refer to cancer or diseases of the circulation such as strokes, heart attacks, atherosclerosis or pulmonary embolisms. Let me remind you of the 'genetic component' of these commoner diseases. It is now abundantly clear that somatic mutations in specific oncogenes correlate with particular cancers. They are clearly one important factor in the cause of malignancy. And, turning to the circulatory disorders, we now know that inherited defects in the low-density lipoprotein receptors are present in patients with a genetic predisposition to atherosclerosis. Genetic factors, whether inherited or acquired by mutation during our lifetime, are therefore important contributory factors to these diseases, but are clearly not the only component. For example, other factors such as diet, or whether one exercises, or one's hormone balance will be among the factors that affect the formation of atheromatous plaque, an early 'indicator' of circulatory problems. Clearly the medical profession has to take 'genetic disease' seriously if we are to learn more about i t and eventually cure it. In haemophilia, the subject of my lecture, we have none of these complications of a multifactorial cause of disease. Haemophilia, whether the A or B form, is caused by an inherited defect in a single X-linked gene, and the disease has the characteristic feature of all X-linked recessives in that it affects boys but not girls. Although unaffected, girls can act as carriers transmitting the disease to future generations. I will suggest to you in this lecture that a study of haemophilia is therefore a good model for understanding the molecular basis of genetic disease as well as for devising better diagnosis and treatment, and for thinking about a cure. I have to admit that other model systems, such as the thalassaemias. have been well studied at the molecular level, but for studies on imporoved treatment and for cure by gene therapy, I suggest that a study of the haemophilias will provide an excellent if challenging model.