Studies on the Origin and Development of Normal Hemagglutinins *

The origin of natural antibodies has been the subject of much controversy over a period of years. Since the extensive investigations by Landois2" on the transfusion of blood, the antibodies from opsonins to those directed against toxins and many infectious agents have been intensively investigated. The scope of investigation has even been extended to cold-blooded animals, revealing hemagglutinins in the blood of turtles,34 alligators,6 and frogs.30 Isohemagglutinins and bacterial agglutinins have also been reported 5' 3 to be present. A great many surveys have been made, which produced evidence for more than one theory of origin. From results of the Schick test performed on more than 150,000 children, .Zingher40 concluded that repeated exposure to infection with the diphtheria bacillus is the most important factor in the development of natural immunity. Parr and Avery25 claim the importance of a racial factor. After a survey of family groups Hirszfeld and his colleagues"6 postulated that immunity or susceptibility to diphtheria is inherited in correlation with blood groups. They believed the blood groups to be constitutional characters and susceptibility to diphtheria to be inherited in correlation with these. It naturally follows that the physiological appearance of antitoxins is also a constitutional character. An external stimulant can prematurely accelerate the formation of antibody only if the physiological capacity exists. This genetic connection between blood group and Schick reaction has been questioned.28 Hirszfeld17 has formulated a theory to account for the occurrence of normal antibodies. He regarded normal antibodies as biochemical organs whose formation is a serological reflex; just as reflexes such as sucking, etc., occur in many animals, so also many normal antibodies occur in the serum without specific stimulation. This occurs at certain times during the life of the individual, and this process of serological maturation was called serogenesis, in analogy to morphogenesis. Before serological maturity has been reached, an antigenic stimulus remains without any