242 M. R. IRWIN 



Landsteiner and Levine (1927) announced the discovery in human cells of 

 a new pair of contrasting antigens, called M and N. These were detectable 

 only by the use of immune sera produced in rabbits, as was another antigenic 

 factor called P. The heritability of the M and N substances is adequately 

 explained by the assumption of a single pair of allelic genes, and the sub- 

 stance P appears to be dominant to its absence. 



Another antigenic factor in human blood which has aroused wide interest 

 is the recently discovered Rh substance, or complex, as it might be termed. 

 In 1940, Landsteiner and Wiener (1940) reported that a new antibody, de- 

 rived from a rabbit immunized with the erythrocytes of a rhesus monkey, 

 was reactive with the cells of about 85 per cent of the white population of 

 New York. They gave the name Rh (a contraction of rhesus) to this agglu- 

 tinable property of human cells. As Boyd (1945) aptly states: 



The technic of testing for the new factor was difficult, the best available serums were 

 weak, and had it not been for a remarkable series of discoveries which followed in the next 

 few months, the Rh factor might have aroused no more interest than its practically still- 

 born brethren. . . . 



The Rh factor was shown to be involved in previously unexplained com- 

 plications following transfusions (Wiener and Peters, 1940), but is most 

 widely known for its role as the etiologic agent in the majority of cases 

 of hemolytic disease of the newborn. The proposal was first made by 

 Levine and Stetson (1939) that an antigen in the fetus, foreign to the mother 

 and presumably transmitted by the father, could pass through the placenta 

 and immunize the mother. Later studies implicated the Rh factor as the 

 foreign antigen, and showed that the antibodies developed in the mother may 

 pass back through the placenta and affect the red blood cells of the fetus, 

 before or following birth. Although the majority of cases of hemolytic disease 

 of the newborn may be justly ascribed to Rh incompatibility between the 

 father and mother, there is no satisfactory explanation as to why only about 

 one in forty of such potentially dangerous combinations leads to morbidity. 



There exist several subgroups, or subtypes, of the Rh complex, and inves- 

 tigations as to their respective specificities occupy the center of interest of 

 many workers at the present writing. There are two schools of thought as to 

 the mode of inheritance of these subgroups, which also involves the terminol- 

 ogy to be used in their identification (see Strandskov, 1948, 1949, for leading 

 references). One explanation is that the various subtypes are manifestations 

 of a series of multiple allelic genes, the other that they are the result of the 

 action of respective genes at three different but closely linked loci. It is not 

 within the province of this chapter to discuss the arguments for and against 

 these two proposals. However, it should be stated that the genetic results 

 under either explanation are essentially the same. 



One of the most pertinent statements which can be made about these 

 various antigenic substances of the erythrocytes is that they are detectable 



