Inheritance, Genes, and Chromosomes

In the Middle Eastern desert 1,800 years ago, a rabbi faced a dilemma. A Jewish woman had given birth to a son. As required by Jewish custom, the mother brought her 8-day-old son to the rabbi for ritual penile circumcision. The rabbi knew that the woman’s two previous sons had bled to death when their foreskins were cut. Yet the biblical requirement remained: unless he was circumcised, the boy could not be counted among those with whom their God had made a solemn covenant. After consultation with other rabbis, the religious leaders decided to exempt this third son.

Almost 1,000 years later, in the twelfth century, the physician and biblical commentator Moses Maimonides reviewed this and other cases in the rabbinical literature and stated that in such instances the third son should not be circumcised. Furthermore, the exemption should apply whether the mother’s son was “from her first husband or from her second husband.” The bleeding disorder, he reasoned, was clearly carried by the mother and passed on to her sons. In all cases, the parents did not show any evidence of having the disease.

Without any knowledge of modern concepts of genes and genetics, the rabbis had linked a human disease with a pattern of inheritance. We now have a name for the disease: it is hemophilia, which affects about 18,000 people in the United States, almost all of them males. The bleeding disorder is due to the absence of a specific protein that is crucial for the formation of blood clots. When a person who does not have hemophilia gets a cut there is usually some bleeding, but soon a clot forms and prevents further bleeding. In the case of hemophilia, no clot forms and the bleeding can continue until the person dies. Indeed, well into the twentieth century the slightest accident could be lethal for such a person. Internal bleeding is also an extremely serious problem for people with this disease, and permanent joint damage due to bleeding in the joints is a common problem for untreated patients.

Treatment of hemophilia by injection of clotting factor into the bloodstream is now possible because the proteins can be isolated from donated blood or made in the laboratory using biotechnological techniques. An issue has been whether people who suffer from hemophilia should receive injections of clotting factor all the time as a preventive measure (an expensive proposition), or only when the factor is needed. Based on reductions in joint damage in children treated by the former (preventive) approach, recent studies have concluded that this approach is best.